The frequencies of HLA class I (HLA-A, B, C) and class II (HLA-DR, DQ) antigens were measured in 107 unrelated schizophrenic subjects and the results compared with 264 controls from south-east Scotland and a second control group of 133 individuals from north-east England. The expression of HLA-B35 was significantly reduced in the schizophrenic population compared to both control populations and these differences remained significant after correction for multiple testing. Linkage of schizophrenia and the major histocompatibility complex region of chromosome 6p was, however, excluded in a group of 17 families multiply affected with schizophrenia. Linkage was also excluded with several red cell antigens, red cell enzymes and plasma proteins. A negative association between the frequency of an HLA antigen and schizophrenia suggests that immune mechanisms may contribute to the aetiology of the disease in some subjects.