We investigated the association between human leukocyte antigens (HLA) and schizophrenia. Fifty-three Caucasian schizophrenic inpatients were tissue-typed. Subjects were tested for 23 type A, 43 type B, four type C, and 10 type DR HLA antigens. Comparison of the schizophrenic group to a group of 114 healthy, Caucasian, potential kidney donors revealed a significantly greater prevalence of two HLA antigens, A 1 and B37, in the schizophrenics. We derived a relative risk for schizophrenia of 2.07 with HLA-A 1 present and 6.88 with HLAB37 present. The antigen combination, Al-B37, while uncommon, was significantly more prevalent in schizophrenics than controls, with a relative risk of 15.87 for schizophrenia with HLA Al-B37 present. Possible mechanisms of association include linkage of HLA genes to loci that code for schizophrenia, mediation of an immune response resulting in schizophrenia, and the interaction of HLA surface antigens on neurons in neurotransmission.