The direct effect of insulin on the secretion of insulin (as measured by C-peptide), glucagon, gastric inhibitory polypeptide, and gastrin was studied in normal subjects by infusing insulin while the plasma level of glucose was maintained in the normal fasting range (euglycemic clamp). Insulin-induced hypoglycemia resulted in increases in circulating glucagon and gastric inhibitory polypeptide, a decrease in C-peptide, and no change in gastrin levels. In contrast, during the euglycemic clamp, insulin was found to behave a direct suppressive effect on the secretion of glucagon, C-peptide, and gastrin, but no effect on levels of gastric inhibitory polypeptide.