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Little is known about the role of the gastric phase in the postprandial pancreaticobiliary response. We evaluated the effect of antral distension on pancreatic, biliary, and gastric secretions and on the release of cholecystokinin (CCK), gastrin, and pancreatic polypeptide in five healthy volunteers. Studies were performed using a duodenal tube with an inflatable balloon in the antrum and a separate gastric tube. Outputs were compared with responses to a maximal CCK stimulus (caerulein), and the role of cholinergic mechanisms was investigated using atropine. Graded antral distension by 50-, 200-, and 350-ml balloon volumes and constant antral distension by 350 ml elicited a marked stimulation of pancreaticobiliary secretions. Mean lipase outputs amounted to 52-60%, and mean bilirubin outputs reached 14-22% of maximal. Atropine completely abolished pancreaticobiliary responses to antral distension. Antral distension did not affect bicarbonate and gastric secretions. Plasma pancreatic polypeptide levels increased markedly during antral distension, and this effect was completely suppressed by atropine. There were no changes in circulating gastrin and CCK. These data demonstrate that antral distension with already small volumes of 50 ml elicits a hitherto unknown potent stimulatory effect, indicating a major role of the antrum in the postprandial pancreaticobiliary response in humans, which is mediated by cholinergic mechanisms.