Autoimmune diseases aggregate in individuals and within pedigrees, and it has been postulated that autoimmune mechanisms may account for a proportion of schizophrenia. Structured questionnaires were used to interview the mothers of 121 DSM-III-R schizophrenic patients and the mothers of 116 controls in order to determine the prevalence of schizophrenia and of autoimmune diseases in their pedigrees. Patients with a schizophrenic first degree relative were significantly more likely to also have a parent or sibling with an autoimmune disease (60% vs. 20%, OR = 6.1, 95% CI = 2.3-6.5, p = 0.0003). A significant excess of insulin dependent diabetes mellitus (IDDM) was present in the parents and siblings of schizophrenic patients (OR = 9.65, 95% CI = 1.3-429.2, p = 0.009). These findings suggest that autoimmune mechanisms may play a role in the aetiology of schizophrenia, particularly familial schizophrenia. Associations have been established between autoimmune diseases and the HLA encoding genes of the major histocompatibility complex on chromosome six, and it may be that some of the genetic liability to schizophrenia involves these genes.