Immune response genes^1,2 of the murine major histocompatibility complex encode cell-surface glycoproteins that are expressed predominantly on B cells and macrophages and regulate immune responsiveness by restricting antigen recognition by T cells. The two classes of immune response molecule, termed I-A and I-E, are each comprised of two polymorphic chains (α and β), and nucleotide sequence analysis of genomic or cDNA clones has revealed that most of the amino acid differences between allelic I-A α or β chains occur in the first extracellular domain^3,4. The mutant mouse strain B6.C-H-2^bm12 (bm12), which differs from its parental strain C57BL/6 (B6) at the I-Aβ locus^5–14, exhibits an immune response profile markedly different from that of B6. Here we present the nucleotide sequence of the mutant bm12 I-Aβ gene. Sequence comparison within the coding regions reveals three productive nucleotide differences between the I-Aβ genes of B6 and bm12 mice, all three differences occurring within a stretch of 14 nucleotides in the exon encoding the first extracellular domain. The clustered nature of the bm12 mutation, as well as the specific amino acid changes it engenders, suggest a possible mechanism for the generation of polymorphism in class II antigens.