Plasma fibrinopeptide A (FPA) concentration, as a measure of thrombin activity, was determined during an insulin tolerance test in 17 non-obese diabetics. FPA was measured by a modification of the Nossel method. Administration of insulin significantly lowered plasma glucose, accompanied by a significant increase in FPA from 0.9 +/- 0.1 ng/ml to 4.3 +/- 1.6 ng/ml (P less than 0.05) as well as a significant increase in circulating levels of epinephrine and growth hormone. The magnitude of the peak in epinephrine levels correlated well with both the rate of decline of plasma glucose and the magnitude of the peak of FPA. In addition, the FPA increment was suppressed by treatment with heparin. These results indicate that insulin-induced hypoglycemia or a rapid fall in plasma glucose is associated with enhanced thrombin generation and fibrin formation, which may be considered as a contributory factor to the development of diabetic microangiopathy through a hypercoagulable state.