We have studied an otherwise normal group of morbidly obese subjects and compared them with patients who had experienced massive weight loss after loop gastric bypass. Compared to normal controls (NLCs), morbidly obese control patients (OBCs) had abnormal glucose tolerance curves (after glucose ingestion), elevated basal insulin levels, and increased plasma insulin concentrations, suggesting insulin insensitivity. The latter has been corroborated by the measurement of decreased insulin binding in these patients. Postoperative (PO) patients were hyperglycemic after taking oral glucose, but all PO patients had a rapid decrease in plasma glucose concentration, half reaching hypoglycemic levels. PO basal insulin levels and insulin receptor number were not statistically different from those in NLCs, indicating up-regulation of insulin receptors (and therefore, increased insulin sensitivity) postoperatively. Hyperinsulinemia seen in the PO group (greater than that in OBCs, P less than 0.001) after administration of oral glucose occurred simultaneously with a doubling of plasma concentration of gastric inhibitory polypeptide. Massive weight loss in patients after gastric bypass was accompanied by an improvement in insulin receptor number, basal hyperinsulinemia, and glucose tolerance. In addition, postoperative patients demonstrated symptomatic reactive hypoglycemia which may have resulted from the hyperinsulinemia seen subsequent to ingestion of glucose.