The products of the highly polymorphic genes known as the major histocompatibility complex (MHC) have been shown to play a major part in the control of several aspects of the immune response and of susceptibility to certain diseases. The major transplantation antigens are membrane proteins composed of two noncovalently associated polypeptide chains: a light, non-polymorphic chain of molecular weight 12,000 (MW), called beta 2-microglobulin, and a polymorphic, glycosylated heavy chain of approximately 45,000 MW. The heavy chains in man and mouse are encoded in at least three loci of the MHC named HLA-A, -B and -C, and H-2D, K and L respectively. The available amino acid sequence data indicate extensive homology between human and mouse heavy chains. We therefore used a recently isolated cloned mouse H-2 cDNA probe to screen a human gene library. We have now characterized one of the recombinant phages obtained, lambda HLA-12, and shown that it contains an authentic HLA sequence with evidence of a second one close by.