To investigate the role of gastric inhibitory polypeptide (GIP) in the hypersecretion of glucose-stimulated insulin release in duodenal ulcer disease, serum glucose, insulin, and immunoreactive GIP (IR-GIP) were measured in 18 healthy subjects and 10 duodenal ulcer patients after glucose ingestion. Although the serum glucose and insulin were significantly greater (P less than 0.05) at 15 and 60 min in the ulcer group, the total integrated glucose areas were similar (20,552 +/- 837 vs. 19,154 +/- 745 mg-min/ml). In contrast, the total integrated insulin area was significantly greater (P less than 0.05) in the ulcer patients (12,873 +/- 2,082 vs. 8,216 +/- 1,072 micro U-min/ml). Mean IR-GIP levels were significantly greater (P less than 0.05) in the ulcer group at 15-120 min of the study, as was the total integrated area (244,755 +/- 34,934 vs. 126,595 +/- 17,468 pg-min/ml). The exaggerated insulin release to oral glucose may be due to the synergistic action of higher blood glucose and greater IR-GIP release in this disease.