A 15 year follow-up study of diabetic patients was performed in Osaka, Japan. The subjects studied were 1939 patients with non-insulin dependent diabetes mellitus (NIDDM), of whom 1000 (51.5%) were alive, 880 (45.4%) had died and 59 (3.0%) were untraceable at the end of 1993. The mortality rate per 1000 person-years of the subjects increased from 28.94 in 1960-1984 to 35.74 in 1985-1993, but the ratio of numbers of observed to expected deaths (O/E ratio) declined from 1.77 to 1.52 for the corresponding periods, suggesting an improvement in the prognosis for diabetic patients, with the exception of patients 65 years or over at the time of entry. Cerebro-cardiovascular and renal diseases were major causes of death, accounting for 48.4% of all deaths. In particular, disease of the heart was the cause of death in 20.5% of all deaths, cerebrovascular disease in 14.5% and renal disease in 12.0%. The O/E ratio was 11.30 for renal disease, which was remarkably high. The O/E ratios were 1.48 for malignant neoplasms, 3.02 for cancer of the liver and 2.15 for cancer of the pancreas. In the subjects less than 65 years of age at entry, a significant decrease in the O/E ratio for overall deaths, malignant neoplasms, disease of the heart, cerebrovascular disease and renal disease was observed, but no notable difference in the O/E ratio for ischemic heart disease was found between the periods 1960-1984 and 1985-1993. By contrast, in the case of subjects 65 years or more at entry, the O/E ratios for overall deaths, malignant neoplasms, disease of the heart, ischemic heart disease and cerebrovascular disease increased markedly in the later period, while there was a considerable decline in renal disease indicated during this period. The analysis suggested a structural change in causes of death of Japanese diabetic patients in recent years, with a relative increase in ischemic heart disease and a relative decrease in renal disease.