The roles of plasma gastrin and duodenal acidity in duodenal ulcer disease remain unclear. In this pathophysiologic study, plasma gastrin and dual gastro-duodenal pH were measured before, during, and after cephalic stimulation (modified sham feeding) and the ingestion of a meal in 16 duodenal ulcer (DU) patients and twelve healthy subjects. Gastrin levels were significantly higher in DU patients both in the fasting state (42.5 ng/l vs. 22.5 ng/l, p less than 0.001) and after the meal (130 vs. 60, p less than 0.02). Two separate patient subsets were identified: a "hypergastrinemic" (HRG) group exhibiting exaggerated gastrin responses and a "Normogastrinemic" (NOG) group comprised of patients with gastrin levels similar to those of controls. Only the HRG group exhibited a significant gastrin response to sham feeding. Both patient groups exhibited a delayed onset of duodenal acidity and delayed peak acid response after feeding indicative of delayed gastric emptying of the acid load. The HRG group exhibited a longer duodenal acid exposure and a prolonged return to premeal pH levels, suggesting a defective switch-off mechanism of acid secretion after duodenal acidification.