A systematic 20-year follow-up study of 1,221 diabetic patients was carried out in Osaka, Japan. The mean annual mortality rates were 2.55% for men and 1.64% for women. The ratios of observed to expected numbers of deaths were 1.50 for men and 1.39 for women, indicating an excess mortality for diabetic patients of both sexes, and higher mortality in men than in women. Factors that predisposed diabetic patients to premature death were early age of onset, albuminuria, diabetic retinopathy and fasting glucose level greater than 11.1 mmol/l at the initial examination. Insulin dependence was also associated with poor prognosis. Cerebro-cardiovascular and renal diseases were the major causes of death in the diabetic patients; heart disease was the cause of death in 16.9%, cerebrovascular disease in 16.4% and renal disease in 11.9%. The relatively high incidence of renal disease as cause of death in diabetic patients was striking. Malignant neoplasms of liver and of pancreas and cirrhosis were also associated with increased ratio of observed to expected number of deaths in the patients.