diff --git a/.gitignore b/.gitignore
index 920a4a7..0332f84 100644
--- a/.gitignore
+++ b/.gitignore
@@ -1,3 +1,5 @@
+/dist
+/quickdna/*.pyd
 /target
 /.hypothesis
 /.vscode
diff --git a/README.md b/README.md
index 6f14353..30b62d2 100644
--- a/README.md
+++ b/README.md
@@ -6,6 +6,8 @@ Quickdna is a simple, fast library for working with DNA sequences. It is up to 1
 translation tasks, in part because it uses a native Rust module (via PyO3) for the translation. However, it exposes
 an easy-to-use, type-annotated API that should still feel familiar for Biopython users.
 
+⚠ *Quickdna is "pre-1.0" software. Its API is still evolving. For now, if you're interested in using quickdna, we suggest you depend on an [exact version](https://python-poetry.org/docs/dependency-specification/#exact-requirements) or [git `rev`](https://python-poetry.org/docs/dependency-specification/#git-dependencies), so that new releases don't break your code.*
+
 ```python
 # These are the two main library types. Unlike Biopython, DnaSequence and
 # ProteinSequence are distinct, though they share a common BaseSequence base class
@@ -55,12 +57,20 @@ ProteinSequence(seq='WLNSLD'), ProteinSequence(seq='G*IVLI'))
 # There is a similar method, `translate_self_frames`, that only returns the
 # (up to 3) translated frames for this direction, without the reverse complement
 
-# The IUPAC ambiguity code 'N' is supported as well.
+# The IUPAC ambiguity codes are supported as well.
 # Codons with N will translate to a specific amino acid if it is unambiguous,
 # such as GGN -> G, or the ambiguous amino acid code 'X' if there are multiple
 # possible translations.
 >>> DnaSequence("GGNATN").translate()
 ProteinSequence(seq='GX')
+
+# The fine-grained ambiguity codes like "R = A or G" are accepted too, and
+# translation results are the same as Biopython. In the output, amino acid
+# ambiguity code 'B' means "either asparagine or aspartic acid" (N or D).
+>>> DnaSequence("RAT").translate()
+ProteinSequence(seq='B')
+
+# To disallow ambiguity codes in translation, try: `.translate(strict=True)`
 ```
 
 ## Benchmarks
@@ -91,10 +101,6 @@ reverse_complement_biopython(covid_genome) | 0.02928ms / iter | 121.55%
   * It's not yet 1.0 -- the API is liable to change in the future.
   * It doesn't support reading FASTA files or many of the other tasks Biopython can do,
     so you'll probably end up still using Biopython or something else to do those tasks.
-  * It doesn't support the (rarer) IUPAC ambiguity codes like B for non-A nucleotides,
-    instead only supporting the general N ambiguity code.
-      * If support for these codes is important to you, please make an issue! It may be possible
-        to support them, it just isn't a priority right now.
 
 ## Installation
 
diff --git a/quickdna/__init__.py b/quickdna/__init__.py
index 7313d35..000d08d 100644
--- a/quickdna/__init__.py
+++ b/quickdna/__init__.py
@@ -1,6 +1,6 @@
 import typing as ty
 
-from .quickdna import _translate, _reverse_complement  # type: ignore
+from .quickdna import _translate, _translate_strict, _reverse_complement, _reverse_complement_strict  # type: ignore
 
 T = ty.TypeVar("T", bound="BaseSequence")
 
@@ -102,22 +102,31 @@ class ProteinSequence(BaseSequence):
 
 class DnaSequence(BaseSequence):
     """
-    A DNA sequence is a sequence of A, T, C, G, or N (ambiguous) nucleotide ASCII bytes.
+    A DNA sequence is a sequence of A, T, C, G, or IUPAC nucleotide ambiguity code ASCII bytes.
     """
 
-    def translate(self, table: int = 1) -> ProteinSequence:
+    def translate(self, table: int = 1, strict: bool = False) -> ProteinSequence:
         """
         Translate a DNA sequence into a protein sequence, using the specified
         NCBI table ID.
 
         Raises ValueError if the table argument is invalid or any characters in
         this sequence are invalid nucleotides.
+
+        If `strict` is true, then the input must be all `ATCG`, with no
+        ambiguous nucleotides. Otherwise, a ValueError is raised.
         """
 
-        seq = _translate(table, self._seq)
+        if strict:
+            seq = _translate_strict(table, self._seq)
+        else:
+            seq = _translate(table, self._seq)
+
         return ProteinSequence(seq)
 
-    def translate_self_frames(self, table: int = 1) -> ty.List[ProteinSequence]:
+    def translate_self_frames(
+        self, table: int = 1, strict: bool = False
+    ) -> ty.List[ProteinSequence]:
         """
         Translate this DNA sequence into up to 3 protein sequences, one for each possible
         reading frame on this sense.
@@ -127,27 +136,32 @@ def translate_self_frames(self, table: int = 1) -> ty.List[ProteinSequence]:
         and a sequence of length 2 has none.
 
         Can raise ValueError, see `self.translate()`
+
+        If `strict` is true, then the input must be all `ATCG`, with no
+        ambiguous nucleotides. Otherwise, a ValueError is raised.
         """
 
         if len(self) >= 5:
             return [
-                self.translate(table),
-                self[1:].translate(table),
-                self[2:].translate(table),
+                self.translate(table, strict),
+                self[1:].translate(table, strict),
+                self[2:].translate(table, strict),
             ]
         elif len(self) == 4:
             return [
-                self.translate(table),
-                self[1:].translate(table),
+                self.translate(table, strict),
+                self[1:].translate(table, strict),
             ]
         elif len(self) == 3:
             return [
-                self.translate(table),
+                self.translate(table, strict),
             ]
         else:
             return []
 
-    def translate_all_frames(self, table: int = 1) -> ty.List[ProteinSequence]:
+    def translate_all_frames(
+        self, table: int = 1, strict: bool = False
+    ) -> ty.List[ProteinSequence]:
         """
         Translate this DNA sequence into at most 6 protein sequences, one for each possible
         reading frame on this sense and the reverse complement.
@@ -157,21 +171,32 @@ def translate_all_frames(self, table: int = 1) -> ty.List[ProteinSequence]:
         and a sequence of length 2 has none.
 
         Can raise ValueError, see `self.translate()`
+
+        If `strict` is true, then the input must be all `ATCG`, with no
+        ambiguous nucleotides. Otherwise, a ValueError is raised.
         """
 
         return [
-            *self.translate_self_frames(table=table),
-            *self.reverse_complement().translate_self_frames(table=table),
+            *self.translate_self_frames(table=table, strict=strict),
+            *self.reverse_complement().translate_self_frames(
+                table=table, strict=strict
+            ),
         ]
 
-    def reverse_complement(self) -> "DnaSequence":
+    def reverse_complement(self, strict: bool = False) -> "DnaSequence":
         """
         Takes the reverse complement of a DNA sequence.
 
         Raises ValueError if any character in this sequence is an invalid nucleotide.
+
+        If `strict` is true, then the input must be all `ATCG`, with no
+        ambiguous nucleotides. Otherwise, a ValueError is raised.
         """
 
-        seq = _reverse_complement(self._seq)
+        if strict:
+            seq = _reverse_complement_strict(self._seq)
+        else:
+            seq = _reverse_complement(self._seq)
         return DnaSequence(seq)
 
 
diff --git a/src/bin/gen_table.rs b/src/bin/gen_table.rs
index 49123d5..4eb6c8c 100644
--- a/src/bin/gen_table.rs
+++ b/src/bin/gen_table.rs
@@ -2,11 +2,11 @@
 //! Should be run from the repository root.
 //! Translation table via Wikipedia.
 
-use std::fs;
+use std::{collections::HashSet, fs};
 
 use quickdna::{
     trans_table::{CodonIdx, TranslationTable},
-    Codon, Nucleotide,
+    CodonAmbiguous, Nucleotide, NucleotideAmbiguous, NucleotideLike,
 };
 
 // via https://en.wikipedia.org/wiki/List_of_genetic_codes
@@ -77,45 +77,36 @@ GGA || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G |
 GGG || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G || G
 ";
 
-fn codon_first_n_index(codon: Codon) -> Option<usize> {
-    let codon: [Nucleotide; 3] = codon.into();
-    codon
-        .iter()
-        .enumerate()
-        .find_map(|(idx, &n)| if n == Nucleotide::N { Some(idx) } else { None })
-}
-
 fn ambiguous_codon_protein(
-    codon: Codon,
+    codon: CodonAmbiguous,
     table_idx: usize,
-    translation_tables: [u8; TranslationTable::LOOKUP_SIZE],
+    translation_tables: &[u8; TranslationTable::LOOKUP_SIZE],
 ) -> u8 {
-    match codon.count(Nucleotide::N) {
-        0 => panic!("not an ambigious codon: {}", codon),
-        1 => {
-            // try and see if all possible permutations of this codon map to the same protein
-            let mut seen_protein = None;
-            let n_index = codon_first_n_index(codon).unwrap();
-
-            for possible in [Nucleotide::A, Nucleotide::T, Nucleotide::C, Nucleotide::G] {
-                let mut candidate: [Nucleotide; 3] = codon.into();
-                candidate[n_index] = possible;
-                let codon_idx: usize = CodonIdx::from(candidate).into();
+    let mut seen_proteins: HashSet<u8> = HashSet::new();
+
+    for &n1 in codon.0[0].possibilities() {
+        for &n2 in codon.0[1].possibilities() {
+            for &n3 in codon.0[2].possibilities() {
+                let codon_idx: usize = CodonIdx::from([n1, n2, n3]).into();
                 let candidate_protein =
                     translation_tables[table_idx * TranslationTable::CODONS_PER_TABLE + codon_idx];
 
-                match seen_protein {
-                    None => {
-                        seen_protein = Some(candidate_protein);
-                    }
-                    Some(p) if p == candidate_protein => {}
-                    _ => return b'X',
+                seen_proteins.insert(candidate_protein);
+                if seen_proteins.len() >= 3 {
+                    return b'X';
                 }
             }
-
-            seen_protein.unwrap()
         }
-        // all codons with 2 or more Ns always map to X
+    }
+
+    let mut seen_vec: Vec<u8> = seen_proteins.into_iter().collect();
+    seen_vec.sort();
+
+    match seen_vec.as_slice() {
+        [single] => *single,
+        [b'D', b'N'] => b'B', // B = Asx = Asparagine or Aspartic acid
+        [b'E', b'Q'] => b'Z', // Z = Glx = Glutamine or Glutamic acid
+        [b'I', b'L'] => b'J', // J = Xle = Leucine or Isoleucine
         _ => b'X',
     }
 }
@@ -141,15 +132,16 @@ fn gen_translation_tables() -> [u8; TranslationTable::LOOKUP_SIZE] {
     }
 
     // setup ambiguous codons
-    for &a in Nucleotide::NUCLEOTIDES.iter() {
-        for &b in Nucleotide::NUCLEOTIDES.iter() {
-            for &c in Nucleotide::NUCLEOTIDES.iter() {
-                if a == Nucleotide::N || b == Nucleotide::N || c == Nucleotide::N {
-                    let codon = Codon([a, b, c]);
+    for a in NucleotideAmbiguous::ALL {
+        for b in NucleotideAmbiguous::ALL {
+            for c in NucleotideAmbiguous::ALL {
+                if a.is_ambiguous() || b.is_ambiguous() || c.is_ambiguous() {
+                    let codon = CodonAmbiguous([a, b, c]);
                     let codon_idx: usize = CodonIdx::from(codon).into();
 
                     for table_idx in 0..TranslationTable::N_TRANS_TABLES {
-                        let protein = ambiguous_codon_protein(codon, table_idx, translation_tables);
+                        let protein =
+                            ambiguous_codon_protein(codon, table_idx, &translation_tables);
                         translation_tables
                             [table_idx * TranslationTable::CODONS_PER_TABLE + codon_idx] = protein;
                     }
@@ -164,4 +156,5 @@ fn gen_translation_tables() -> [u8; TranslationTable::LOOKUP_SIZE] {
 fn main() {
     let tables = gen_translation_tables();
     fs::write("src/tables.dat", tables).expect("failed to write tables.dat");
+    println!("Wrote codon translation table data to src/tables.dat.");
 }
diff --git a/src/errors.rs b/src/errors.rs
index 86a946f..04dc18e 100644
--- a/src/errors.rs
+++ b/src/errors.rs
@@ -8,6 +8,8 @@ pub enum TranslationError {
     NonAsciiChar(char),
     #[error("bad nucleotide: {:?}", .0)]
     BadNucleotide(char),
+    #[error("unexpected ambiguous nucleotide: {:?}", .0)]
+    UnexpectedAmbiguousNucleotide(char),
     #[error("not a ncbi translation table: {}", .0)]
     BadTranslationTable(u8),
 }
diff --git a/src/fasta.rs b/src/fasta.rs
index bebf047..afc7cee 100644
--- a/src/fasta.rs
+++ b/src/fasta.rs
@@ -57,7 +57,7 @@ pub struct FastaParseSettings {
     ///         FastaRecord {
     ///             header: "b".to_string(),
     ///             contents: "...".to_string(),
-    ///             line_range: (2, 4),        
+    ///             line_range: (2, 4),
     ///         }
     ///     ],
     /// );
@@ -72,7 +72,7 @@ pub struct FastaParseSettings {
     ///             header: "a\nb".to_string(),
     ///             contents: "...".to_string(),
     ///             line_range: (1, 4),
-    ///         }  
+    ///         }
     ///     ],
     /// );
     /// ```
@@ -93,7 +93,7 @@ pub struct FastaParseSettings {
     ///         FastaRecord {
     ///             header: "a".to_string(),
     ///             contents: "sequence".to_string(),
-    ///             line_range: (2, 4),        
+    ///             line_range: (2, 4),
     ///         }
     ///     ]
     /// );
@@ -112,7 +112,7 @@ pub struct FastaParseSettings {
     ///         FastaRecord {
     ///             header: "a".to_string(),
     ///             contents: "sequence".to_string(),
-    ///             line_range: (2, 4),        
+    ///             line_range: (2, 4),
     ///         }
     ///     ]
     /// );
@@ -459,7 +459,7 @@ fn try_parse_header(line: &str) -> Option<&str> {
 mod tests {
     use super::*;
 
-    use crate::{DnaSequence, ProteinSequence, TranslationError};
+    use crate::{DnaSequence, Nucleotide, NucleotideAmbiguous, ProteinSequence, TranslationError};
     use std::time::Duration;
 
     macro_rules! assert_parse {
@@ -1123,7 +1123,7 @@ mod tests {
     fn test_dna_fasta() {
         assert_parse!(
             ">Virus1\nAAAA",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
             vec![FastaRecord {
                 header: "Virus1".to_string(),
                 contents: "AAAA".parse().unwrap(),
@@ -1132,11 +1132,35 @@ mod tests {
         );
     }
 
+    #[test]
+    fn test_dna_fasta_ambiguous() {
+        assert_parse!(
+            ">Virus1\nABCD",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
+            vec![FastaRecord {
+                header: "Virus1".to_string(),
+                contents: "ABCD".parse().unwrap(),
+                line_range: (1, 3),
+            }]
+        );
+    }
+
+    #[test]
+    fn test_dna_fasta_strict() {
+        // Strict as in "when parsing Nucleotide, disallow ambiguity codes".
+        // No relation to the FastaParser `strict()` call.
+        assert_parse_err!(
+            ">Virus1\nABCD",
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
+            FastaParseError::ParseError(TranslationError::UnexpectedAmbiguousNucleotide('B'))
+        );
+    }
+
     #[test]
     fn test_dna_fasta_multiple() {
         assert_parse!(
             ">Virus1\nAAAA\nAAAA\n>Virus2\nCCCC\nCCCC\n",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
             vec![
                 FastaRecord {
                     header: "Virus1".to_string(),
@@ -1150,13 +1174,29 @@ mod tests {
                 },
             ]
         );
+        assert_parse!(
+            ">Virus1\nAAAA\nAAAA\n>Virus2\nCCCC\nRRRR\n",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
+            vec![
+                FastaRecord {
+                    header: "Virus1".to_string(),
+                    contents: "AAAAAAAA".parse().unwrap(),
+                    line_range: (1, 4),
+                },
+                FastaRecord {
+                    header: "Virus2".to_string(),
+                    contents: "CCCCRRRR".parse().unwrap(),
+                    line_range: (4, 7),
+                },
+            ]
+        );
     }
 
     #[test]
     fn test_dna_dna_whitespace() {
         assert_parse!(
             ">Virus1\nAAAA \n",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
             vec![FastaRecord {
                 header: "Virus1".to_string(),
                 contents: "AAAA".parse().unwrap(),
@@ -1165,11 +1205,11 @@ mod tests {
         );
 
         assert_parse!(
-            ">Virus1\n  AAAA\t\t\n",
-            FastaParser::<DnaSequence>::strict(),
+            ">Virus1\n  AAAA\tBCD \t\n",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
             vec![FastaRecord {
                 header: "Virus1".to_string(),
-                contents: "AAAA".parse().unwrap(),
+                contents: "AAAABCD".parse().unwrap(),
                 line_range: (1, 3),
             }]
         );
@@ -1179,7 +1219,12 @@ mod tests {
     fn test_dna_invalid_dna() {
         assert_parse_err!(
             ">Virus1\nAAAelephant",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
+            FastaParseError::ParseError(TranslationError::BadNucleotide('e'))
+        );
+        assert_parse_err!(
+            ">Virus1\nAAAelephant",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
             FastaParseError::ParseError(TranslationError::BadNucleotide('e'))
         );
     }
@@ -1188,7 +1233,12 @@ mod tests {
     fn test_dna_invalid_dna_multiple() {
         assert_parse_err!(
             ">Virus1\nAAAA\n>Virus2\nAAAAelephant",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
+            FastaParseError::ParseError(TranslationError::BadNucleotide('e'))
+        );
+        assert_parse_err!(
+            ">Virus1\nAAAA\n>Virus2\nAAAAelephant",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
             FastaParseError::ParseError(TranslationError::BadNucleotide('e'))
         );
     }
@@ -1197,7 +1247,12 @@ mod tests {
     fn test_dna_invalid_dna_unicode() {
         assert_parse_err!(
             ">Virus1\nAAčCCG\n",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
+            FastaParseError::ParseError(TranslationError::NonAsciiByte(196))
+        );
+        assert_parse_err!(
+            ">Virus1\nAAčCCG\n",
+            FastaParser::<DnaSequence<NucleotideAmbiguous>>::strict(),
             FastaParseError::ParseError(TranslationError::NonAsciiByte(196))
         );
     }
@@ -1239,7 +1294,7 @@ mod tests {
     fn test_duplicate_header_lines() {
         assert_parse!(
             ">Virus1\nAAAA\nAAAA\n>Virus1\nCCCC\nCCCC\n",
-            FastaParser::<DnaSequence>::strict(),
+            FastaParser::<DnaSequence<Nucleotide>>::strict(),
             vec![
                 FastaRecord {
                     header: "Virus1".to_string(),
diff --git a/src/nucleotide.rs b/src/nucleotide.rs
index 89e633e..168f6dc 100644
--- a/src/nucleotide.rs
+++ b/src/nucleotide.rs
@@ -2,23 +2,90 @@ use std::fmt::{self, Write};
 
 use crate::errors::TranslationError;
 
-/// A DNA nucleotide, or the IUPAC ambiguity code 'N'.
+/// A DNA nucleotide.
 ///
-/// Sorts in ATCGN order, not alphabetical.
+/// Sorts in ATCG order, not alphabetical.
 #[derive(Debug, Clone, Copy, PartialEq, Eq, PartialOrd, Ord, std::hash::Hash)]
 #[repr(u8)]
 pub enum Nucleotide {
-    A = 0,
-    T = 1,
-    C = 2,
-    G = 3,
-    /// IUPAC ambiguity code
-    N = 4,
+    A = 0b0001,
+    T = 0b0010,
+    C = 0b0100,
+    G = 0b1000,
 }
 
+/// A DNA nucleotide, or an IUPAC ambiguity code representing a set of possible nucleotides.
+#[derive(Debug, Clone, Copy, PartialEq, Eq, PartialOrd, Ord, std::hash::Hash)]
+#[repr(u8)]
+pub enum NucleotideAmbiguous {
+    A = Nucleotide::A as u8,
+    T = Nucleotide::T as u8,
+    C = Nucleotide::C as u8,
+    G = Nucleotide::G as u8,
+
+    W = Nucleotide::A as u8 | Nucleotide::T as u8,
+    M = Nucleotide::A as u8 | Nucleotide::C as u8,
+    R = Nucleotide::A as u8 | Nucleotide::G as u8, // purines
+    Y = Nucleotide::T as u8 | Nucleotide::C as u8, // pyrimidines
+    S = Nucleotide::C as u8 | Nucleotide::G as u8,
+    K = Nucleotide::T as u8 | Nucleotide::G as u8,
+
+    B = Nucleotide::T as u8 | Nucleotide::C as u8 | Nucleotide::G as u8, // not A
+    V = Nucleotide::A as u8 | Nucleotide::C as u8 | Nucleotide::G as u8, // not T
+    D = Nucleotide::A as u8 | Nucleotide::T as u8 | Nucleotide::G as u8, // not C
+    H = Nucleotide::A as u8 | Nucleotide::T as u8 | Nucleotide::C as u8, // not G
+
+    N = Nucleotide::A as u8 | Nucleotide::T as u8 | Nucleotide::C as u8 | Nucleotide::G as u8,
+}
+
+pub trait NucleotideLike:
+    Copy + Eq + Into<u8> + Into<char> + TryFrom<u8, Error = TranslationError>
+{
+    fn complement(self) -> Self;
+    fn bits(self) -> u8;
+    fn to_ascii(self) -> u8;
+    fn is_ambiguous(self) -> bool;
+}
+
+const fn ascii_to_nucleotide_table() -> [Option<NucleotideAmbiguous>; 256] {
+    // PERF: This was previously a 128-byte array, with "high" bytes eliminated
+    // by a separate check. But extending it to 256 elements makes Rust realize
+    // it's safe to index with any u8-cast-to-usize and eliminate a bounds check
+    // from the generated code.
+    let mut pack_table = [None; 256];
+
+    macro_rules! insert {
+        ($chr:literal, $variant:expr) => {
+            pack_table[$chr.to_ascii_uppercase() as usize] = Some($variant);
+            pack_table[$chr.to_ascii_lowercase() as usize] = Some($variant);
+        };
+    }
+
+    insert!(b'a', NucleotideAmbiguous::A);
+    insert!(b't', NucleotideAmbiguous::T);
+    insert!(b'c', NucleotideAmbiguous::C);
+    insert!(b'g', NucleotideAmbiguous::G);
+
+    // ambiguity codes
+    insert!(b'n', NucleotideAmbiguous::N); // A, T, C, or G (complement N)
+    insert!(b'm', NucleotideAmbiguous::M); // A or C (complement K)
+    insert!(b'r', NucleotideAmbiguous::R); // A or G (complement Y)
+    insert!(b'w', NucleotideAmbiguous::W); // A or T (complement W, itself)
+    insert!(b's', NucleotideAmbiguous::S); // C or G (complement S, itself)
+    insert!(b'y', NucleotideAmbiguous::Y); // C or T (complement R)
+    insert!(b'k', NucleotideAmbiguous::K); // G or T (complement M)
+    insert!(b'v', NucleotideAmbiguous::V); // A, C or G (complement B)
+    insert!(b'h', NucleotideAmbiguous::H); // A, C or T (complement D)
+    insert!(b'd', NucleotideAmbiguous::D); // A, G or T (complement H)
+    insert!(b'b', NucleotideAmbiguous::B); // C, G or T (complement V)
+
+    pack_table
+}
+
+const ASCII_TO_NUCLEOTIDE: [Option<NucleotideAmbiguous>; 256] = ascii_to_nucleotide_table();
+
 impl Nucleotide {
-    pub const NUCLEOTIDES: [Self; 5] = [Self::A, Self::T, Self::C, Self::G, Self::N];
-    const N_NUCLEOTIDES: u8 = Self::NUCLEOTIDES.len() as u8;
+    pub const ALL: [Self; 4] = [Self::A, Self::T, Self::C, Self::G];
 
     pub const PURINES: [Self; 2] = [Self::A, Self::G];
     pub const PYRIMIDINES: [Self; 2] = [Self::C, Self::T];
@@ -26,59 +93,160 @@ impl Nucleotide {
     pub const M_AMBIGUITY: [Self; 2] = [Self::A, Self::C];
     pub const R_AMBIGUITY: [Self; 2] = Self::PURINES;
     pub const W_AMBIGUITY: [Self; 2] = [Self::A, Self::T];
-
     pub const S_AMBIGUITY: [Self; 2] = [Self::C, Self::G];
     pub const Y_AMBIGUITY: [Self; 2] = Self::PYRIMIDINES;
-
     pub const K_AMBIGUITY: [Self; 2] = [Self::G, Self::T];
 
     pub const V_AMBIGUITY: [Self; 3] = [Self::A, Self::C, Self::G];
     pub const H_AMBIGUITY: [Self; 3] = [Self::A, Self::C, Self::T];
     pub const D_AMBIGUITY: [Self; 3] = [Self::A, Self::G, Self::T];
     pub const B_AMBIGUITY: [Self; 3] = [Self::C, Self::G, Self::T];
+}
+
+impl NucleotideLike for Nucleotide {
+    fn complement(self) -> Self {
+        match self {
+            Self::A => Self::T,
+            Self::T => Self::A,
+            Self::C => Self::G,
+            Self::G => Self::C,
+        }
+    }
+
+    fn bits(self) -> u8 {
+        self as u8
+    }
+
+    fn to_ascii(self) -> u8 {
+        match self {
+            Self::A => b'A',
+            Self::T => b'T',
+            Self::C => b'C',
+            Self::G => b'G',
+        }
+    }
 
-    const fn ascii_pack_table() -> [u8; 128] {
-        let mut pack_table = [255u8; 128];
+    fn is_ambiguous(self) -> bool {
+        false
+    }
+}
 
-        macro_rules! insert {
-            ($chr:literal, $variant:expr) => {
-                pack_table[$chr.to_ascii_uppercase() as usize] = $variant as u8;
-                pack_table[$chr.to_ascii_lowercase() as usize] = $variant as u8;
-            };
+impl NucleotideAmbiguous {
+    pub const ALL: [Self; 15] = [
+        Self::A,
+        Self::T,
+        Self::W,
+        Self::C,
+        Self::M,
+        Self::Y,
+        Self::H,
+        Self::G,
+        Self::R,
+        Self::K,
+        Self::D,
+        Self::S,
+        Self::V,
+        Self::B,
+        Self::N,
+    ];
+
+    pub const fn possibilities(self) -> &'static [Nucleotide] {
+        match self {
+            Self::A => &[Nucleotide::A],
+            Self::T => &[Nucleotide::T],
+            Self::C => &[Nucleotide::C],
+            Self::G => &[Nucleotide::G],
+            Self::W => &[Nucleotide::A, Nucleotide::T],
+            Self::M => &[Nucleotide::A, Nucleotide::C],
+            Self::R => &[Nucleotide::A, Nucleotide::G],
+            Self::Y => &[Nucleotide::T, Nucleotide::C],
+            Self::S => &[Nucleotide::C, Nucleotide::G],
+            Self::K => &[Nucleotide::T, Nucleotide::G],
+            Self::B => &[Nucleotide::T, Nucleotide::C, Nucleotide::G],
+            Self::V => &[Nucleotide::A, Nucleotide::C, Nucleotide::G],
+            Self::D => &[Nucleotide::A, Nucleotide::T, Nucleotide::G],
+            Self::H => &[Nucleotide::A, Nucleotide::T, Nucleotide::C],
+            Self::N => &[Nucleotide::A, Nucleotide::T, Nucleotide::C, Nucleotide::G],
         }
+    }
+}
 
-        insert!(b'a', Self::A);
-        insert!(b't', Self::T);
-        insert!(b'c', Self::C);
-        insert!(b'g', Self::G);
+impl NucleotideLike for NucleotideAmbiguous {
+    fn complement(self) -> Self {
+        match self {
+            Self::A => Self::T,
+            Self::T => Self::A,
+            Self::W => Self::W,
+            Self::C => Self::G,
+            Self::M => Self::K,
+            Self::Y => Self::R,
+            Self::H => Self::D,
+            Self::G => Self::C,
+            Self::R => Self::Y,
+            Self::K => Self::M,
+            Self::D => Self::H,
+            Self::S => Self::S,
+            Self::V => Self::B,
+            Self::B => Self::V,
+            Self::N => Self::N,
+        }
+    }
 
-        // ambiguity codes (all mapped to N for now)
-        insert!(b'n', Self::N); // A, T, C, or G (complement N)
-        insert!(b'm', Self::N); // A or C (complement K)
-        insert!(b'r', Self::N); // A or G (complement Y)
-        insert!(b'w', Self::N); // A or T (complement W (self))
-        insert!(b's', Self::N); // C or G (complement S (self))
-        insert!(b'y', Self::N); // C or T (complement R)
-        insert!(b'k', Self::N); // G or T (complement M)
-        insert!(b'v', Self::N); // A, C or G (complement B)
-        insert!(b'h', Self::N); // A, C or T (complement D)
-        insert!(b'd', Self::N); // A, G or T (complement H)
-        insert!(b'b', Self::N); // C, G or T (complement V)
+    fn bits(self) -> u8 {
+        self as u8
+    }
 
-        pack_table
+    fn to_ascii(self) -> u8 {
+        match self {
+            Self::A => b'A',
+            Self::T => b'T',
+            Self::W => b'W',
+            Self::C => b'C',
+            Self::M => b'M',
+            Self::Y => b'Y',
+            Self::H => b'H',
+            Self::G => b'G',
+            Self::R => b'R',
+            Self::K => b'K',
+            Self::D => b'D',
+            Self::S => b'S',
+            Self::V => b'V',
+            Self::B => b'B',
+            Self::N => b'N',
+        }
     }
 
-    const ASCII_PACK_TABLE: [u8; 128] = Self::ascii_pack_table();
+    fn is_ambiguous(self) -> bool {
+        (self as usize).count_ones() > 1
+    }
+}
 
-    const COMPLEMENT_TABLE: [Self; Self::N_NUCLEOTIDES as usize] =
-        [Self::T, Self::A, Self::G, Self::C, Self::N];
-    pub const fn complement(self) -> Self {
-        Self::COMPLEMENT_TABLE[self as u8 as usize]
+impl From<Nucleotide> for NucleotideAmbiguous {
+    #[inline(always)]
+    fn from(value: Nucleotide) -> Self {
+        match value {
+            Nucleotide::A => Self::A,
+            Nucleotide::T => Self::T,
+            Nucleotide::C => Self::C,
+            Nucleotide::G => Self::G,
+        }
     }
+}
 
-    const ASCII_MAP: [u8; Self::N_NUCLEOTIDES as usize] = [b'A', b'T', b'C', b'G', b'N'];
-    pub const fn to_ascii(self) -> u8 {
-        Self::ASCII_MAP[self as usize]
+impl TryFrom<NucleotideAmbiguous> for Nucleotide {
+    type Error = TranslationError;
+
+    #[inline(always)]
+    fn try_from(value: NucleotideAmbiguous) -> Result<Self, Self::Error> {
+        match value {
+            NucleotideAmbiguous::A => Ok(Self::A),
+            NucleotideAmbiguous::T => Ok(Self::T),
+            NucleotideAmbiguous::C => Ok(Self::C),
+            NucleotideAmbiguous::G => Ok(Self::G),
+            other => Err(TranslationError::UnexpectedAmbiguousNucleotide(
+                other.into(),
+            )),
+        }
     }
 }
 
@@ -87,17 +255,29 @@ impl TryFrom<u8> for Nucleotide {
 
     #[inline(always)]
     fn try_from(u: u8) -> Result<Self, Self::Error> {
-        if u < 128 {
-            let v = Self::ASCII_PACK_TABLE[u as usize];
-            if v < Self::N_NUCLEOTIDES {
-                // SAFETY: there are only X variants, with assigned numbers, so 0..=(X - 1)
-                //         are valid reprs of this type
-                Ok(unsafe { std::mem::transmute(v) })
-            } else {
-                Err(TranslationError::BadNucleotide(u.into()))
-            }
-        } else {
-            Err(TranslationError::NonAsciiByte(u))
+        if u >= 128 {
+            return Err(TranslationError::NonAsciiByte(u));
+        }
+
+        match ASCII_TO_NUCLEOTIDE[u as usize] {
+            Some(na) => Nucleotide::try_from(na),
+            None => Err(TranslationError::BadNucleotide(u.into())),
+        }
+    }
+}
+
+impl TryFrom<u8> for NucleotideAmbiguous {
+    type Error = TranslationError;
+
+    #[inline(always)]
+    fn try_from(u: u8) -> Result<Self, Self::Error> {
+        if u >= 128 {
+            return Err(TranslationError::NonAsciiByte(u));
+        }
+
+        match ASCII_TO_NUCLEOTIDE[u as usize] {
+            Some(na) => Ok(na),
+            None => Err(TranslationError::BadNucleotide(u.into())),
         }
     }
 }
@@ -114,46 +294,33 @@ impl From<Nucleotide> for char {
     }
 }
 
-impl fmt::Display for Nucleotide {
-    fn fmt(&self, f: &mut fmt::Formatter<'_>) -> fmt::Result {
-        f.write_char((*self).into())
+impl From<NucleotideAmbiguous> for u8 {
+    fn from(n: NucleotideAmbiguous) -> Self {
+        n.to_ascii()
     }
 }
 
-#[derive(Debug, Clone, Copy, PartialEq, Eq, std::hash::Hash)]
-pub struct Codon(pub [Nucleotide; 3]);
-
-impl Codon {
-    /// How many of the specified nucleotide this codon includes
-    pub fn count(&self, n: Nucleotide) -> usize {
-        let mut count = 0;
-        if self.0[0] == n {
-            count += 1
-        }
-        if self.0[1] == n {
-            count += 1
-        }
-        if self.0[2] == n {
-            count += 1
-        }
-        count
+impl From<NucleotideAmbiguous> for char {
+    fn from(n: NucleotideAmbiguous) -> Self {
+        n.to_ascii() as char
     }
+}
 
-    /// Whether the codon includes `N`
-    pub fn is_ambiguous(&self) -> bool {
-        self.count(Nucleotide::N) > 0
+impl fmt::Display for Nucleotide {
+    fn fmt(&self, f: &mut fmt::Formatter<'_>) -> fmt::Result {
+        f.write_char((*self).into())
     }
+}
 
-    /// Returns an iterator of all codons, including ambiguous codons with `N`
-    pub fn all_codons() -> impl Iterator<Item = Self> {
-        const N: [Nucleotide; 5] = Nucleotide::NUCLEOTIDES;
-        N.iter().flat_map(move |&a| {
-            N.iter()
-                .flat_map(move |&b| N.iter().map(move |&c| Codon([a, b, c])))
-        })
+impl fmt::Display for NucleotideAmbiguous {
+    fn fmt(&self, f: &mut fmt::Formatter<'_>) -> fmt::Result {
+        f.write_char((*self).into())
     }
 }
 
+#[derive(Debug, Clone, Copy, PartialEq, Eq, std::hash::Hash)]
+pub struct Codon(pub [Nucleotide; 3]);
+
 impl TryFrom<[u8; 3]> for Codon {
     type Error = TranslationError;
 
@@ -177,3 +344,43 @@ impl fmt::Display for Codon {
         write!(f, "{}{}{}", self.0[0], self.0[1], self.0[2])
     }
 }
+
+#[derive(Debug, Clone, Copy, PartialEq, Eq, std::hash::Hash)]
+pub struct CodonAmbiguous(pub [NucleotideAmbiguous; 3]);
+
+impl TryFrom<[u8; 3]> for CodonAmbiguous {
+    type Error = TranslationError;
+
+    fn try_from(value: [u8; 3]) -> Result<Self, Self::Error> {
+        Ok(Self([
+            NucleotideAmbiguous::try_from(value[0])?,
+            NucleotideAmbiguous::try_from(value[1])?,
+            NucleotideAmbiguous::try_from(value[2])?,
+        ]))
+    }
+}
+
+impl From<CodonAmbiguous> for [NucleotideAmbiguous; 3] {
+    fn from(c: CodonAmbiguous) -> Self {
+        c.0
+    }
+}
+
+impl fmt::Display for CodonAmbiguous {
+    fn fmt(&self, f: &mut fmt::Formatter<'_>) -> fmt::Result {
+        write!(f, "{}{}{}", self.0[0], self.0[1], self.0[2])
+    }
+}
+
+impl CodonAmbiguous {
+    pub fn possibilities(&self) -> impl Iterator<Item = Codon> + '_ {
+        self.0[0].possibilities().iter().flat_map(move |&a| {
+            self.0[1].possibilities().iter().flat_map(move |&b| {
+                self.0[2]
+                    .possibilities()
+                    .iter()
+                    .map(move |&c| Codon([a, b, c]))
+            })
+        })
+    }
+}
diff --git a/src/python_api.rs b/src/python_api.rs
index 774744e..12b876e 100644
--- a/src/python_api.rs
+++ b/src/python_api.rs
@@ -5,6 +5,7 @@ use pyo3::{exceptions::PyValueError, prelude::*, types::PyBytes};
 use crate::{
     errors::TranslationError,
     trans_table::{reverse_complement_bytes, TranslationTable},
+    Nucleotide, NucleotideAmbiguous,
 };
 
 impl From<TranslationError> for PyErr {
@@ -19,16 +20,52 @@ fn _check_table(table: u8) -> PyResult<()> {
     Ok(())
 }
 
+/// Translate a bytestring of DNA nucleotides into a bytestring of amino acids.
+///
+/// The input string is allowed to contain IUPAC ambiguity codes; ambiguous
+/// codons are represented by `X` in the output.
+///
+/// * `translate(b"CCNTACACK CATNCNAAT")` returns `b"PYTHXN"`
 #[pyfunction]
 fn _translate(py: Python, table: u8, dna: &PyBytes) -> PyResult<PyObject> {
     let table = TranslationTable::try_from(table)?;
-    let bytes = table.translate_dna_bytes(dna.as_bytes())?;
+    let bytes = table.translate_dna_bytes::<NucleotideAmbiguous>(dna.as_bytes())?;
     Ok(PyBytes::new(py, &bytes).into())
 }
 
+/// Translate a bytestring of DNA nucleotides into a bytestring of amino acids.
+///
+/// The input string is validated to consist of unambiguous nucleotides (no IUPAC ambiguity codes).
+///
+/// * `translate_strict(b"AAACCCTTTGGG")` returns `b"KPFG"`
+/// * `translate_strict(b"AAACCCTTTGGN")` is an error.
+#[pyfunction]
+fn _translate_strict(py: Python, table: u8, dna: &PyBytes) -> PyResult<PyObject> {
+    let table = TranslationTable::try_from(table)?;
+    let bytes = table.translate_dna_bytes::<Nucleotide>(dna.as_bytes())?;
+    Ok(PyBytes::new(py, &bytes).into())
+}
+
+/// Get the reverse complement of a bytestring of DNA nucleotides.
+///
+/// The input string is allowed to contain IUPAC ambiguity codes.
+///
+/// * `reverse_complement(b"AAAAABCCC")` returns `b"GGGVTTTTT"`
 #[pyfunction]
 fn _reverse_complement(py: Python, dna: &PyBytes) -> PyResult<PyObject> {
-    let bytes = reverse_complement_bytes(dna.as_bytes())?;
+    let bytes = reverse_complement_bytes::<NucleotideAmbiguous>(dna.as_bytes())?;
+    Ok(PyBytes::new(py, &bytes).into())
+}
+
+/// Get the reverse complement of a bytestring of DNA nucleotides.
+///
+/// The input string is validated to consist of unambiguous nucleotides (no IUPAC ambiguity codes).
+///
+/// * `reverse_complement_strict(b"AAAAAACCC")` returns `b"GGGTTTTTT"`
+/// * `reverse_complement_strict(b"AAAAAACCN")` is an error.
+#[pyfunction]
+fn _reverse_complement_strict(py: Python, dna: &PyBytes) -> PyResult<PyObject> {
+    let bytes = reverse_complement_bytes::<Nucleotide>(dna.as_bytes())?;
     Ok(PyBytes::new(py, &bytes).into())
 }
 
@@ -36,7 +73,9 @@ fn _reverse_complement(py: Python, dna: &PyBytes) -> PyResult<PyObject> {
 fn quickdna(_py: Python, m: &PyModule) -> PyResult<()> {
     m.add_function(wrap_pyfunction!(_check_table, m)?)?;
     m.add_function(wrap_pyfunction!(_translate, m)?)?;
+    m.add_function(wrap_pyfunction!(_translate_strict, m)?)?;
     m.add_function(wrap_pyfunction!(_reverse_complement, m)?)?;
+    m.add_function(wrap_pyfunction!(_reverse_complement_strict, m)?)?;
 
     Ok(())
 }
diff --git a/src/rust_api.rs b/src/rust_api.rs
index baaed7f..c419f53 100644
--- a/src/rust_api.rs
+++ b/src/rust_api.rs
@@ -5,7 +5,9 @@ use std::str::FromStr;
 use smallvec::SmallVec;
 
 pub use crate::errors::TranslationError;
-pub use crate::nucleotide::{Codon, Nucleotide};
+pub use crate::nucleotide::{
+    Codon, CodonAmbiguous, Nucleotide, NucleotideAmbiguous, NucleotideLike,
+};
 pub use crate::trans_table::TranslationTable;
 
 use crate::trans_table::reverse_complement;
@@ -134,13 +136,13 @@ impl FromStr for ProteinSequence {
 }
 
 #[derive(Debug, Clone, PartialEq, Eq, PartialOrd, Ord, std::hash::Hash)]
-pub struct DnaSequence {
-    dna: Vec<Nucleotide>,
+pub struct DnaSequence<T: NucleotideLike> {
+    dna: Vec<T>,
 }
 
-impl DnaSequence {
+impl<T: NucleotideLike> DnaSequence<T> {
     /// Construct a new DnaSequence from a Vec of nucleotides
-    pub fn new(dna: Vec<Nucleotide>) -> Self {
+    pub fn new(dna: Vec<T>) -> Self {
         Self { dna }
     }
 
@@ -211,13 +213,13 @@ impl DnaSequence {
         self.dna.windows(length).map(|w| Self::new(w.to_vec()))
     }
 
-    pub fn push(&mut self, n: Nucleotide) {
+    pub fn push(&mut self, n: T) {
         self.dna.push(n);
     }
 }
 
-impl BaseSequence for DnaSequence {
-    type Item = Nucleotide;
+impl<T: NucleotideLike> BaseSequence for DnaSequence<T> {
+    type Item = T;
 
     fn as_slice(&self) -> &[Self::Item] {
         &self.dna
@@ -228,9 +230,10 @@ impl BaseSequence for DnaSequence {
     }
 }
 
-impls!(DnaSequence);
+impls!(DnaSequence<Nucleotide>);
+impls!(DnaSequence<NucleotideAmbiguous>);
 
-impl fmt::Display for DnaSequence {
+impl<T: NucleotideLike> fmt::Display for DnaSequence<T> {
     fn fmt(&self, f: &mut fmt::Formatter<'_>) -> fmt::Result {
         for &n in &self.dna {
             f.write_char(n.into())?;
@@ -239,7 +242,7 @@ impl fmt::Display for DnaSequence {
     }
 }
 
-impl TryFrom<&[u8]> for DnaSequence {
+impl<T: NucleotideLike> TryFrom<&[u8]> for DnaSequence<T> {
     type Error = TranslationError;
 
     fn try_from(value: &[u8]) -> Result<Self, Self::Error> {
@@ -248,14 +251,14 @@ impl TryFrom<&[u8]> for DnaSequence {
 
         for &b in value {
             if b != b' ' && b != b'\t' {
-                vec.push(Nucleotide::try_from(b)?);
+                vec.push(T::try_from(b)?);
             }
         }
         Ok(Self::new(vec))
     }
 }
 
-impl TryFrom<Vec<u8>> for DnaSequence {
+impl<T: NucleotideLike> TryFrom<Vec<u8>> for DnaSequence<T> {
     type Error = TranslationError;
 
     fn try_from(value: Vec<u8>) -> Result<Self, Self::Error> {
@@ -263,7 +266,7 @@ impl TryFrom<Vec<u8>> for DnaSequence {
     }
 }
 
-impl FromStr for DnaSequence {
+impl<T: NucleotideLike> FromStr for DnaSequence<T> {
     type Err = TranslationError;
 
     fn from_str(s: &str) -> Result<Self, Self::Err> {
@@ -284,7 +287,11 @@ mod tests {
         };
     }
 
-    fn dna(dna: &str) -> DnaSequence {
+    fn dna(dna: &str) -> DnaSequence<NucleotideAmbiguous> {
+        DnaSequence::from_str(dna).unwrap()
+    }
+
+    fn dna_strict(dna: &str) -> DnaSequence<Nucleotide> {
         DnaSequence::from_str(dna).unwrap()
     }
 
@@ -302,7 +309,7 @@ mod tests {
     fn test_dna_parses() {
         for c in 0_u8..128 {
             let c = char::from(c);
-            let r = DnaSequence::from_str(&String::from(c));
+            let r = DnaSequence::<NucleotideAmbiguous>::from_str(&String::from(c));
             if "aAtTcCgGmMrRwWsSyYkKvVhHdDbBnN \t".chars().any(|x| x == c) {
                 assert!(
                     r.is_ok(),
@@ -317,12 +324,48 @@ mod tests {
         }
     }
 
+    #[test]
+    fn test_dna_parses_strict() {
+        for c in 0_u8..128 {
+            let c = char::from(c);
+            let r = DnaSequence::<Nucleotide>::from_str(&String::from(c));
+            if "aAtTcCgG \t".chars().any(|x| x == c) {
+                assert!(
+                    r.is_ok(),
+                    "{c:?} should be a valid nucleotide, or allowed whitespace"
+                );
+            } else {
+                assert!(
+                    r.is_err(),
+                    "{c:?} should *not* be a valid nucleotide, or allowed whitespace"
+                );
+            }
+        }
+    }
+
     #[test]
     fn test_translate() {
         assert_eq!(
             dna("AAAGGGAAA").translate(TranslationTable::Ncbi1),
             protein("KGK")
         );
+        assert_eq!(
+            dna_strict("AAAGGGAAA").translate(TranslationTable::Ncbi1),
+            protein("KGK")
+        );
+    }
+
+    #[test]
+    fn test_translate_ambiguous() {
+        // R means "A or G" and both {TTA,TTG} map to L (Leucine).
+        // Thus, "TTR" should map to L.
+        //
+        // But V means "A or G or C", and TTC maps to F (Phenylalanine).
+        // Thus, "TTV" is truly ambiguous and maps to X.
+        assert_eq!(
+            dna("TTR TTV").translate(TranslationTable::Ncbi1),
+            protein("LX")
+        );
     }
 
     #[test]
@@ -332,6 +375,11 @@ mod tests {
             dna("AAAGGGAAA").translate_self_frames(TranslationTable::Ncbi1),
             smallvec![protein("KGK"), protein("KG"), protein("RE"),]
         );
+        assert_eq_smallvec!(
+            3,
+            dna_strict("AAAGGGAAA").translate_self_frames(TranslationTable::Ncbi1),
+            smallvec![protein("KGK"), protein("KG"), protein("RE"),]
+        );
     }
 
     #[test]
@@ -361,6 +409,33 @@ mod tests {
             .is_empty());
     }
 
+    #[test]
+    fn test_short_translate_self_strict() {
+        assert_eq_smallvec!(
+            3,
+            dna_strict("GGGG").translate_self_frames(TranslationTable::Ncbi1),
+            smallvec![protein("G"), protein("G"),]
+        );
+
+        assert_eq_smallvec!(
+            3,
+            dna_strict("GGG").translate_self_frames(TranslationTable::Ncbi1),
+            smallvec![protein("G"),]
+        );
+
+        assert!(dna_strict("GG")
+            .translate_self_frames(TranslationTable::Ncbi1)
+            .is_empty());
+
+        assert!(dna_strict("G")
+            .translate_self_frames(TranslationTable::Ncbi1)
+            .is_empty());
+
+        assert!(dna_strict("")
+            .translate_self_frames(TranslationTable::Ncbi1)
+            .is_empty());
+    }
+
     #[test]
     fn test_translate_all() {
         assert_eq_smallvec!(
@@ -375,6 +450,18 @@ mod tests {
                 protein("SL"),
             ]
         );
+        assert_eq_smallvec!(
+            6,
+            dna_strict("AAAGGGAAA").translate_all_frames(TranslationTable::Ncbi1),
+            smallvec![
+                protein("KGK"),
+                protein("KG"),
+                protein("RE"),
+                protein("FPF"),
+                protein("FP"),
+                protein("SL"),
+            ]
+        );
     }
 
     #[test]
@@ -404,6 +491,33 @@ mod tests {
             .is_empty());
     }
 
+    #[test]
+    fn test_short_translate_all_strict() {
+        assert_eq_smallvec!(
+            6,
+            dna_strict("GGGG").translate_all_frames(TranslationTable::Ncbi1),
+            smallvec![protein("G"), protein("G"), protein("P"), protein("P"),]
+        );
+
+        assert_eq_smallvec!(
+            6,
+            dna_strict("GGG").translate_all_frames(TranslationTable::Ncbi1),
+            smallvec![protein("G"), protein("P"),]
+        );
+
+        assert!(dna_strict("GG")
+            .translate_all_frames(TranslationTable::Ncbi1)
+            .is_empty());
+
+        assert!(dna_strict("G")
+            .translate_all_frames(TranslationTable::Ncbi1)
+            .is_empty());
+
+        assert!(dna_strict("")
+            .translate_all_frames(TranslationTable::Ncbi1)
+            .is_empty());
+    }
+
     #[test]
     fn test_dna_equality() {
         let d1 = dna("aaa");
@@ -414,6 +528,16 @@ mod tests {
         assert_eq!(d1, d3);
     }
 
+    #[test]
+    fn test_dna_equality_strict() {
+        let d1 = dna_strict("aaa");
+        let d2 = dna_strict("aaa");
+        let d3 = dna_strict("aAa");
+
+        assert_eq!(d1, d2);
+        assert_eq!(d1, d3);
+    }
+
     #[test]
     fn test_protein_equality() {
         let p1 = protein("aaa");
@@ -428,6 +552,14 @@ mod tests {
     fn test_protein_case() {
         assert_eq!(dna("GGG").translate(TranslationTable::Ncbi1), protein("g"));
         assert_eq!(dna("GGG").translate(TranslationTable::Ncbi1), protein("G"));
+        assert_eq!(
+            dna_strict("GGG").translate(TranslationTable::Ncbi1),
+            protein("g")
+        );
+        assert_eq!(
+            dna_strict("GGG").translate(TranslationTable::Ncbi1),
+            protein("G")
+        );
     }
 
     #[test]
@@ -442,6 +574,18 @@ mod tests {
         assert_eq!(hash(&p1), hash(&p2));
     }
 
+    #[test]
+    fn test_hash_strict() {
+        let d1 = dna_strict("aaa");
+        let d2 = dna_strict("aaa");
+        let p1 = protein("aaa");
+        let p2 = protein("aaa");
+
+        assert_eq!(hash(&d1), hash(&d2));
+        assert!(hash(&d1) != hash(&p1));
+        assert_eq!(hash(&p1), hash(&p2));
+    }
+
     #[test]
     fn test_dna_windows() {
         let d = dna("gcantacctaangtnattag");
@@ -465,6 +609,29 @@ mod tests {
         assert_eq!(dna("antg").windows(10).next(), None);
     }
 
+    #[test]
+    fn test_dna_windows_strict() {
+        let d = dna_strict("gcactacctaacgtcattag");
+        assert_eq!(
+            d.windows(10).collect::<Vec<_>>(),
+            vec![
+                dna_strict("gcactaccta"),
+                dna_strict("cactacctaa"),
+                dna_strict("actacctaac"),
+                dna_strict("ctacctaacg"),
+                dna_strict("tacctaacgt"),
+                dna_strict("acctaacgtc"),
+                dna_strict("cctaacgtca"),
+                dna_strict("ctaacgtcat"),
+                dna_strict("taacgtcatt"),
+                dna_strict("aacgtcatta"),
+                dna_strict("acgtcattag"),
+            ]
+        );
+
+        assert_eq!(dna_strict("actg").windows(10).next(), None);
+    }
+
     #[test]
     fn test_protein_windows() {
         let p = protein("gcantacctaangtnattag");
@@ -495,6 +662,10 @@ mod tests {
         dna("  gcantac\tctaangtnattag ");
         dna(" gca ntac ctaangtnattag \t");
 
+        dna_strict("gcactacctaacgtcattag ");
+        dna_strict("  gcactac\tctaacgtcattag ");
+        dna_strict(" gca ctac ctaacgtcattag \t");
+
         protein("angtnattag ");
         protein(" angtnattag ");
         protein(" an  gtnattag \t");
diff --git a/src/tables.dat b/src/tables.dat
index 369ac5e..b107575 100644
--- a/src/tables.dat
+++ b/src/tables.dat
@@ -1 +1 @@
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TTT***SSSKX***XXXXX****************************YY*X***LFFLX***SSSSS***WCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX****************************YY*X***LFFLX***SSSSS***GCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX****************************YY*X***LFFLX***SSSSS****CCWX***XXXXX***************************QHHQX***LLLAX***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX***************************QYYQX***LFFLX***SSSSS***WCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX***************************QYYQX***LFFLX***SSSSS***WCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX***************************YYYYY***LFFLX***SSSSS****CCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX***************************EYYEX***LFFLX***SSSSS****CCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX***************************EYYEX***LFFLX***SSSSS***WCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***RSSRX***XXXXX****************************YYWX***LFFLX***SSSSS****CCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXXKNNKX***IIIMX***TTTTT***SSSKX***XXXXX***************************YYY*X***LFFLX***SSSSS***WCCWX***XXXXX***************************QHHQX***LLLLL***PPPPP***RRRRR***XXXXX***************************EDDEX***VVVVV***AAAAA***GGGGG***XXXXX***************************XXXXX***XXXXX***XXXXX***XXXXX***XXXXX
\ No newline at end of file
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\ No newline at end of file
diff --git a/src/trans_table.rs b/src/trans_table.rs
index b88373a..c5517fb 100644
--- a/src/trans_table.rs
+++ b/src/trans_table.rs
@@ -1,48 +1,83 @@
 use crate::{
     errors::TranslationError,
-    nucleotide::{Codon, Nucleotide},
+    nucleotide::{Codon, CodonAmbiguous, NucleotideLike},
 };
 
+/// Identifies a translation table for turning codons into amino acids.
+/// See: https://en.wikipedia.org/wiki/List_of_genetic_codes
 #[derive(Debug, Clone, Copy, PartialEq, Eq)]
 pub enum TranslationTable {
+    /// The standard code
     Ncbi1,
+    /// The vertebrate mitochondrial code
     Ncbi2,
+    /// The yeast mitochondrial code
     Ncbi3,
+    /// The mold, protozoan, and coelenterate mitochondrial code and the mycoplasma/spiroplasma code
     Ncbi4,
+    /// The invertebrate mitochondrial code
     Ncbi5,
+    /// The ciliate, dasycladacean and hexamita nuclear code
     Ncbi6,
+    /// The kinetoplast code; cf. table 4.
     Ncbi7,
+    /// Same as table 1.
     Ncbi8,
+    /// The echinoderm and flatworm mitochondrial code
     Ncbi9,
+    /// The euplotid nuclear code
     Ncbi10,
+    /// The bacterial, archaeal and plant plastid code
     Ncbi11,
+    /// The alternative yeast nuclear code
     Ncbi12,
+    /// The ascidian mitochondrial code
     Ncbi13,
+    /// The alternative flatworm mitochondrial code
     Ncbi14,
+    /// The Blepharisma nuclear code
     Ncbi15,
+    /// The chlorophycean mitochondrial code
     Ncbi16,
+
     // tables 17-20 are not assigned
+    /// The trematode mitochondrial code
     Ncbi21,
+    /// The Scenedesmus obliquus mitochondrial code
     Ncbi22,
+    /// The Thraustochytrium mitochondrial code
     Ncbi23,
+    /// The Pterobranchia mitochondrial code
     Ncbi24,
+    /// The candidate division SR1 and gracilibacteria code
     Ncbi25,
+    /// The Pachysolen tannophilus nuclear code
     Ncbi26,
+    /// The karyorelict nuclear code
     Ncbi27,
+    /// The Condylostoma nuclear code
     Ncbi28,
+    /// The Mesodinium nuclear code
     Ncbi29,
+    /// The Peritrich nuclear code
     Ncbi30,
+    /// The Blastocrithidia nuclear code
     Ncbi31,
+    /// The Balanophoraceae plastid code
     Ncbi32,
+    /// The Cephalodiscidae mitochondrial code
     Ncbi33,
 }
 
 #[repr(transparent)]
 pub struct CodonIdx(usize);
 
-impl From<[Nucleotide; 3]> for CodonIdx {
-    fn from(value: [Nucleotide; 3]) -> Self {
-        Self((value[0] as usize) << 6 | (value[1] as usize) << 3 | (value[2] as usize))
+impl<T: NucleotideLike> From<[T; 3]> for CodonIdx {
+    fn from(value: [T; 3]) -> Self {
+        let v0 = value[0].bits() as usize;
+        let v1 = value[1].bits() as usize;
+        let v2 = value[2].bits() as usize;
+        Self((v0 << 8) | (v1 << 4) | v2)
     }
 }
 
@@ -52,6 +87,12 @@ impl From<Codon> for CodonIdx {
     }
 }
 
+impl From<CodonAmbiguous> for CodonIdx {
+    fn from(c: CodonAmbiguous) -> Self {
+        c.0.into()
+    }
+}
+
 impl From<CodonIdx> for usize {
     fn from(c: CodonIdx) -> Self {
         c.0
@@ -59,9 +100,8 @@ impl From<CodonIdx> for usize {
 }
 
 impl TranslationTable {
-    /// There are really only 125 possible codons (len(ATCGN)^3), but since codons take up
-    /// 3 bits, the maximum codon value is 0b100100100, so we need some holes in the table.
-    pub const CODONS_PER_TABLE: usize = 293;
+    /// Each ambiguity code is represented by 4 bits, so there are (2^4)^3 codons per table.
+    pub const CODONS_PER_TABLE: usize = 1 << 12;
     // Number of NCBI translation tables (they go up to 33, but there's gaps in the numbering)
     pub const N_TRANS_TABLES: usize = 27;
     pub const LOOKUP_SIZE: usize = Self::CODONS_PER_TABLE * Self::N_TRANS_TABLES;
@@ -102,7 +142,10 @@ impl TranslationTable {
         }
     }
 
-    pub fn translate_dna_bytes(self, dna: &[u8]) -> Result<Vec<u8>, TranslationError> {
+    pub fn translate_dna_bytes<T: NucleotideLike>(
+        self,
+        dna: &[u8],
+    ) -> Result<Vec<u8>, TranslationError> {
         if dna.is_empty() {
             return Ok(Vec::new());
         }
@@ -115,9 +158,9 @@ impl TranslationTable {
         // biopython also truncates, but warns -- generally I don't think we care,
         // so I just made it silently truncate
         for chunk in dna.chunks_exact(3) {
-            let a = chunk[0].try_into()?;
-            let b = chunk[1].try_into()?;
-            let c = chunk[2].try_into()?;
+            let a: T = chunk[0].try_into()?;
+            let b: T = chunk[1].try_into()?;
+            let c: T = chunk[2].try_into()?;
             let codon_idx = CodonIdx::from([a, b, c]);
             result.push(
                 Self::TRANSLATION_TABLES
@@ -128,7 +171,7 @@ impl TranslationTable {
         Ok(result)
     }
 
-    pub fn translate_dna(self, dna: &[Nucleotide]) -> Vec<u8> {
+    pub fn translate_dna<T: NucleotideLike>(self, dna: &[T]) -> Vec<u8> {
         if dna.is_empty() {
             return Vec::new();
         }
@@ -141,7 +184,7 @@ impl TranslationTable {
         // biopython also truncates, but warns -- generally I don't think we care,
         // so I just made it silently truncate
         for chunk in dna.chunks_exact(3) {
-            let sized_chunk: [Nucleotide; 3] = [chunk[0], chunk[1], chunk[2]];
+            let sized_chunk: [T; 3] = [chunk[0], chunk[1], chunk[2]];
             let codon_idx = CodonIdx::from(sized_chunk);
             result.push(
                 Self::TRANSLATION_TABLES
@@ -192,19 +235,21 @@ impl TryFrom<u8> for TranslationTable {
     }
 }
 
-pub fn reverse_complement_bytes(dna: &[u8]) -> Result<Vec<u8>, TranslationError> {
+pub fn reverse_complement_bytes<T: NucleotideLike>(
+    dna: &[u8],
+) -> Result<Vec<u8>, TranslationError> {
     let mut v = vec![0u8; dna.len()];
     for (i, &b) in dna.iter().enumerate() {
-        let n = Nucleotide::try_from(b)?;
+        let n = T::try_from(b)?;
         v[dna.len() - 1 - i] = n.complement().to_ascii();
     }
     Ok(v)
 }
 
-pub fn reverse_complement(dna: &[Nucleotide]) -> Vec<Nucleotide> {
-    let mut v = vec![Nucleotide::N; dna.len()];
-    for (i, &n) in dna.iter().enumerate() {
-        v[dna.len() - 1 - i] = n.complement();
-    }
-    v
+// Perf: it looks like .collect() gets great codegen here, but not when dealing
+// with Result as it would in `reverse_complement_bytes` above. Here, it beats
+// writing something like `let mut v = vec![T::default(), dna.len()];` which
+// wastes time doing a memset before filling the Vec.
+pub fn reverse_complement<T: NucleotideLike>(dna: &[T]) -> Vec<T> {
+    dna.iter().rev().map(|n| n.complement()).collect()
 }
diff --git a/tests/test_exhaustive.py b/tests/test_exhaustive.py
index 8c2f9d4..c31decd 100644
--- a/tests/test_exhaustive.py
+++ b/tests/test_exhaustive.py
@@ -7,7 +7,7 @@
 from quickdna import DnaSequence
 from .utils import valid_tables
 
-NUCLEOTIDES = "ATCGN"
+NUCLEOTIDES = "ATCGWMRYSKBVDHN"
 
 
 def test_exhaustive():
@@ -19,4 +19,4 @@ def test_exhaustive():
                     qd_trans = chr(DnaSequence(dna).translate(table=table)[0])
                     bp_trans = str(Seq(dna).translate(table=table))[0]
 
-                    assert qd_trans == bp_trans, dna
+                    assert qd_trans == bp_trans, f"Testing {dna} in table {table}"
diff --git a/tests/test_wrapper.py b/tests/test_wrapper.py
index 8b1790d..edcb312 100644
--- a/tests/test_wrapper.py
+++ b/tests/test_wrapper.py
@@ -135,3 +135,20 @@ def test_iter():
 
     p_src = "kgkg" * 20
     assert list(ProteinSequence(p_src)) == list(p_src)
+
+
+def test_reverse_complement():
+    rc = DnaSequence("AAAGGGGGG").reverse_complement()
+    assert rc == DnaSequence("CCCCCCTTT")
+    rc = DnaSequence("AAABBBGGG").reverse_complement()
+    assert rc == DnaSequence("CCCVVVTTT")
+    with pytest.raises(ValueError):
+        DnaSequence("AAABBBGGG").reverse_complement(strict=True)
+
+
+def test_strict():
+    assert DnaSequence("AAAGGGAAA").translate(table=1, strict=True) == ProteinSequence(
+        "KGK"
+    )
+    with pytest.raises(ValueError):
+        DnaSequence("AAABBBAAA").translate(table=1, strict=True)