The potential role of antecedent viral infection in the pathogenesis of Type 1 (insulin-dependent) diabetes was investigated by measuring antibody titres to several viruses in serum obtained at the time of diagnosis of diabetes. An outbreak of Coxsackie B4 infection followed by a wave of Coxsackie B3 and B5 infections occurred in Seattle during the time viral serology was obtained in the diabetic patients. Antibody titres to Cocksackie B5 and Influenza A and B viruses were comparable in diabetics and matched control subjects, but antibody titres to Cocksackie B3 and B4 were lower in the diabetics and a low antibody titre to Coxsackie B3/B4 was associated with a significantly increased relative risk of diabetes.