The major histocompatibility complex is a chromosomal segment embodying several gene clusters among which those with immune functions are the best characterized. This region is suspected to host other as yet undetected genes whose characterization may shed light on the population genetics and evolution of the whole gene complex and thus on its unexplained character of marker locus for a number of diseases of nonimmune or unknown pathogenesis. A novel gene was identified that is transcribed in all tissues tested and is located in mouse and man between the CA and Bf genes of the H-2 and HLA complexes, respectively. From the nucleotide sequence, derived from liver complementary DNA clones, it is predicted that this novel single-copy gene encodes a 42-kilodalton polypeptide that bears no recognizable relation to the protein families known so far, but it displays striking hallmarks of natural selection.