The mechanisms controlling glucose dynamics and insulin secretion of nine patients with symptomatic postprandial hypoglycemia following subtotal gastrectomy were studied. Following oral administration of glucose, the patients showed early hyperglycemia and late hypoglycemia. Insulin secretion was exaggerated; plasma insulin and glucose responses to intravenously administered glucose, tolbutamide sodium, secretin, and glucagon were either low or normal compared to control subjects. Intravenously administered glucose followed by glucagon also given intravenously 25 minutes later caused an exaggerated insulin secretion and delayed hypoglycemia. In two patients, carbohydrate restriction for several months resulted in unchanged early plasma glucose curves, absent later hypoglycemia, and markedly decreased insulin secretion following oral administration of glucose. Carbohydrate refeeding of one patient reestablished postprandial hypoglycemia and exaggerated insulin secretion. The data suggest that postgastrectomy hypoglycemia is caused by an inducible gastrointestinal factor which potentiates glucose-mediated insulin release.