Using a gastric barostat to measure gastric tone, we previously demonstrated that nutrient perfusion into the intestine induces gastric relaxation. To investigate the pathway of this enterogastric reflex we surgically isolated the vagi either in a cervical skin tunnel (3 dogs) or within an implanted supradiaphragmatic cooling jacket (3 dogs). In the conscious fasted dogs, cervical or supradiaphragmatic vagal blockade by cooling (5 degrees C X 10 min) induced a reversible gastric relaxation. Bethanechol (0.2 mg X kg-1 X h-1 iv) alone or in combination with adrenergic blockers (phentolamine 1.5 mg X kg-1 X h-1 + propranolol 0.3 mg X kg-1 X h-1) suppressed the cooling-induced relaxation but did not abolish gastric relaxation induced by intestinal nutrient perfusion (Osmolite, 3.1 ml/min). At this point, vagal cooling, either cervical or supradiaphragmatic, reversibly blocked the nutrient-induced gastric relaxation: gastric tone significantly increased driven by the cholinergic background and reverted after vagal rewarming to the previous relaxed state. We conclude that intestinal nutrients induce gastric relaxation by a nonadrenergic noncholinergic mechanism. This reflex is mediated by fibers contained in the vagus nerves at both cervical and supradiaphragmatic levels.