The nucleotide sequences of the human class I major histocompatibility complex genes HLA-B27k and HLA-B27w have been determined. They differ by only four nucleotides over a stretch of 14 bp in exon 2, resulting in three amino acid exchanges at positions 77 (Asp to Asn), 80 (Thr to Ile) and 81 (Leu to Ala). The distribution of these nucleotide substitutions suggests a gene conversion-like event responsible for the generation of these HLA-B27 subtypes. The mechanisms underlying the generation of new polymorphic variants in man are therefore probably identical to the gene conversion-like events postulated in the generation of H-2Kbm class I mutants in the mouse.