Islets were evaluated for the presence of amyloid deposits in 169 pancreases removed at autopsy. Islet amyloid occurred in 17 of 142 (12 per cent) of nondiabetics and in 16 of 27 (59 per cent) of diabetics. When diabetics were divided into categories according to clinical severity of disease, the insulin treated diabetics had the highest prevalence (89 per cent), the most diffuse distribution, and the most severe degree of islet amyloidosis. Amyloid was not found in any pancreases from subjects under 40 years of age. Above the age of 40, there was no correlation between aging and prevalence of islet amyloid. There was a significant association between severity of diabetes and prevalence of islet amyloid. The low prevalence of amyloid seen in nondiabetics and the fact that all adult onset, insulin treated diabetics had islet amyloid indicate that a reaction to endogenous insulin may be the basis for the deposition of islet amyloid.