Using a newly developed gastric barostat, we studied the effect of duodenal distention on gastric tone in a chronic canine model. In the conscious, fasted dogs, duodenal distention for 15 s consistently induced a marked gastric relaxation (delta intragastric volume = 226 +/- 23 ml). This response could be induced repeatedly without evidence of fatigue. Neither bethanechol nor combined phentolamine and propranolol infused intravenously had any significant effect on gastric relaxation in response to duodenal distention. To investigate the pathway of this duodenogastric mechanism, in four dogs we isolated the vagal nerves at the supradiaphragmatic level within an implanted cooling jacket. During intravenous infusion of bethanechol (used as a cholinergic background to maintain base-line gastric tone), supradiaphragmatic vagal blockade by cooling abolished the gastric relaxatory response to duodenal distention (delta intragastric volume = 11 +/- 5 ml during vagal blockade vs. 194 +/- 36 after vagal rewarming; P less than 0.05). This effect of acute and reversible vagal blockade by cooling was also mimicked by bilateral surgical vagotomy. We conclude that a nonadrenergic, noncholinergic mechanism participates in gastric relaxation induced by duodenal distention. This mechanism is mediated by the vagus nerve.