Thirty-one patients with subclinical diabetes, who showed diabetic or impaired glucose tolerance after treatment for diabetes, were investigated in order to clarify the abnormalities of insulin response in diabetes mellitus. These patients showed a delayed response of plasma insulin during oral glucose loading. In the tolbutamide-glucose test, in which glucose loading followed the intravenous tolbutamide injection at a 60-min interval, the insulin level at 90 min was significantly lowered in a group of 20 patients with subclinical diabetes. In the tolbutamide-glucagon test, in which 1 mg of glucagon was injected 60 min after tolbutamide injection, the maximal level of plasma insulin was significantly decreased in a group of 10 subclinical diabetes except for one patient. These results indicate that insulinogenesis and/or release of insulin were decreased even in subclinical diabetes, suggesting that such a defect in islet function might be one of the abnormalities in primary diabetes.