Our aim was to determine whether endogenously released gastrin inhibits cyclic interdigestive motility in the proximal stomach. In 4 dogs with chronic duodenal electrodes and isolated innervated antral pouches, we constructed proximal gastric pouches, the external neural connections of which were completely severed by autotransplanting the pouches to the left pelvis. After recovery, the antral pouch was irrigated with 0.2% acetylcholine for 3.7 hr at 90 ml/hr, while intraluminal pressure was monitored in the proximal gastric pouch and myoelectric activity was recorded from the duodenum. Blood was collected concurrently for radioimmunoassay of gastrin. The antral irrigations increased serum gastrin from a mean +/- SEM of 85 +/- 14 pg/ml before irrigation to a mean +/- SEM of 350 +/- 54 pg/ml after 30 min of irrigation (P less than 0.001), and the increased levels continued throughout the remaining 3.2 hr of irrigation. The irrigations also suppressed the cycles of interdigestive motor activity in the proximal gastric pouch and the cycles of interdigestive myoelectric activity in the duodenum. The cycles had a mean duration +/- SEM of 105 +/- 5 min before irrigation in both the proximal gastric pouch and duodenum, but were abolished in every test during irrigation. Irrigation inhibited the cycles even when cimetidine was given intravenously at 200 mg/hr to block gastrin-stimulated secretion of HCl, duodenal acidification, and subsequent release of duodenal hormones. However, cimetidine alone had no effect on the interdigestive cycles. We concluded that antral irrigation with acetylcholine inhibited interdigestive cyclic motility in the proximal stomach via a hormonal mechanism and that gastrin was likely the hormone involved.