To elucidate the role of gastric inhibitory polypeptide (GIP) in the alteration of insulin secretion following pancreatoduodenal resection, in which the main sources of GIP are removed, plasma levels of GIP were measured for 180 minutes after oral glucose administration, both before and after radical pancreatoduodenectomy in nine patients with periampullary cancer. Fasting plasma levels of GIP remained much the same before and after surgery, and were not different from those in normal controls. The levels of GIP after glucose ingestion were significantly greater in the preoperative patients than in normal controls throughout 180 minutes. After pancreatoduodenectomy, the postglucose levels significantly diminished but remained within normal limits. Changes in plasma levels of insulin early after glucose ingestion in these patients, however, were significantly less both before and after surgery than in normal controls, and were not concomitant with the initial increase in plasma GIP. On the other hand, plasma levels of insulin greatly increased immediately after glucose ingestion in accordance with a rapid elevation of plasma GIP in 11 gastrectomized patients in whom the duodenum and the pancreas were preserved intact and who served as the control group. Thus, the diminution in GIP secretion following pancreatoduodenectomy may relate to the lack of main sources of this gut hormone and not to factors involved in the reconstruction of the alimentary tract. We conclude that the impaired insulin secretion following oral glucose ingestion in patients before and after pancreatoduodenectomy does not relate to the secretion of GIP.