Eleven lymphocyte antigens have been defined in cattle using 81 lymphocytotoxic sera. These sera (typing reagents) were selected from over 1,000 normal sera, 35 alloimmune sera, and 111 samples of colostrum whey. Absorptions revealed that nine of the 11 antigens detected by these reagents are serologically independent. Segregation of the genes controlling these antigens was observed among 470 calves from mating of 56 heterozygous sires and 360 dams, indicating that each of the 11 antigens is controlled by one of 11 alleles at a single autosomal co-dominant locus BoLA-A (Bovine Lymphocyte Antigen, locus A). To determine the relation between BoLA antigens and histocompatibility, skin allografts were exchanged among four unrelated adult cows. Incompatibilities for the SD antigens, but not MLR or blood group antigens, were predictive of early rejection of allografts. Furthermore, graft recipients produced antibodies against the SD antigens of incompatible donors. These results indicate that the BoLA-A locus is part of the major histocompatibility complex (MHC) of cattle.