Islet-cell antibodies (I.C.A.) were found in 38% (319/829) of insulin-dependent diabetic patients, in 5% (6/112) of insulin-independent diabetics, and in 1.7% (3/177) of non-diabetic subjects. In the insulin-dependent group I.C.A. were found in 85% of patients immediately after the onset of symptoms and they became less common as the duration of disease increased I.C.A. were equally common in both sexes and the decline in their prevalence was independent of age. The antibodies were directed against cytoplasmic components of islet cells but not against insulin itself. The appearance of I.C.A. probably follows cell damage occurring before the onset of symptoms. By contrast, thyroid and gastric autoantibodies were more common in older patients and females. There was no correlation between the presence of these antibodies and I.C.A. in patients with either diabetes of recent onset or longstanding disease.