We studied the plasma insulin response during a 100 g oral glucose tolerance test (OGTT) in subjects with NIDDM and various other conditions associated with glucose intolerance. The criteria for definite diabetes and previously definite diabetes is proposed for those whose fasting blood glucose (FBG) is, or has been, greater than 140 mg dl⁻¹ in the past. A diabetic type glucose tolerance with FBG lower than 140 mg dl⁻¹ was called 'equivocal diabetes'. Insulin response was almost invariably lower in definite diabetes and previously definite diabetes compared to control groups with similar degree of glucose intolerance even in the states of non‐diabetic glucose tolerance. This was in contrast to other conditions which are often associated with glucose intolerance such as corticosteroid treatment, post‐gastrectomy, liver diseases, in which insulin response is increased with the impairment of glucose tolerance as far as the FBG remains below 140 mg dl⁻¹. The low insulin response in definite diabetes can be represented by a decreased insulinogenic index, the ratio of increment of plasma insulin (μml⁻¹) to that of blood glucose (mg dl⁻¹) 30 min after the glucose load. Insulin response was judged to be low when this index was less than 0.5. Low insulin response was a reproducible feature, better than the category of glucose tolerance. It was highly correlated with acute insulin response (AIR) elicited by intravenous glucose injection. The prevalence of low insulin responders was high among groups with a family history of NIDDM. Diabetes with elevated FBG occurred more frequently in low insulin responders than in normal insulin responders. Fasting and 2‐h insulin levels are lower in definite diabetes than in control groups with similar blood glucose levels. The so‐called inverted‐U shape relationship of plasma insulin to blood glucose was not so apparent in definite diabetes. We conclude that a low insulin response · to oral glucose, as represented by a low insulinogenic index, is an important inherent characteristic in definite diabetes and probably plays a predominant role in the pathogenesis of NIDDM in most Japanese patients.