A total of 1788 non-diabetic subjects, screened by a general health check, had either glycosuria or marginal elevation of fasting blood glucose and/or HbA1c. They were followed by repeated 100 g oral glucose tolerance tests for up to 8 years. Their initial mean age was 52 years and the mean BMI was 23.2. Low insulin secretory response was defined when the insulinogenic index, a ratio of increment of plasma insulin to that of plasma glucose 30 min after oral glucose load, was lower than 0.5. Cumulative incidence of diabetes with fasting blood glucose (FBG) exceeding 120 mg dl-1 was significantly higher in impaired glucose tolerance (IGT) than in non-IGT, and in each of IGT and non-IGT groups, the incidence was significantly higher for low than normal insulin responders. The mean initial plasma insulin response in subjects who developed diabetes was significantly lower than in those who remained non-diabetic with the same category of glucose tolerance at baseline irrespective of the degree of glucose intolerance. The mean baseline BMI did not differ whether or not they developed diabetes, but a few cases who developed diabetes despite normal initial insulin response were much more obese. Fasting insulin levels did not correlate with FBG during the course of development of diabetes. We suggest that defective insulin secretion plays a predominant role in the non-obese subtype of NIDDM which includes the majority of Japanese patients, while both insulin resistance and insulin secretory defect are important in the obese subtype for the development of diabetes.