H-2K, H-2D, H-2I, Qa-2 and TL are all members of a closely related family of cell-surface glycoproteins. The H-2 molecules (major histocompatibility antigens) are extremely polymorphic, expressed on almost all cell types and play an important part in graft rejection1-4. In contrast, Qa-2 and TL are much less polymorphic, and have a limited tissue distribution4,5. Nevertheless, all these molecules are similar in that they consist of two chains, one of which is the invariant beta2-microglobulin (molecular weight (MW) 11,500), the other a 45,000-MW glycopolypeptide2,6-10. The 45,000-MW H-2K and H-2D map within 0.3 centimorgans of each other in the major histocompatibility complex (MHC) on chromosome 17 (ref. 1). The Qa-2 and TL chains are encoded by genes in the closely linked Tla region. Recently, recombinant DNA techniques have been used to study the family of genes encoding H-2-like molecules11-14. The finding that cloned H-2 cDNA hybridizes to 10-20 restriction fragments of genomic DNA has led to the conclusion that there are 10-20 H-2-like genes in the murine genome11,12. Here we present evidence that most of these genes are encoded on chromosome 17 and that at least three H-2-like genes map outside the MHC in the Tla region. We also confirm and provide further evidence that there are 10 to 15 H-2-like genes in the mouse genome.