Several gastrointestinal hormones have been found in the intestinal lumen, but as yet their physiologic role is not yet clear. We have previously shown in anesthesized animals that electrical vagal stimulation provokes simultaneous intraluminal release of serotonin (5-HT) and substance P (SP). The aim of this study was to investigate if a physiologic stimulus, a meal, releases 5-HT, SP, and gastrin (G) into the canine jejunum. In 10 dogs, chronic jejunal Thiry-Vella loops were perfused with saline (37 degrees C) before and after: a test meal; atropine, 0.2 mg/kg intravenously before the meal; atropine alone at the same dose; propanolol, 0.5 mg/kg intravenously before the meal; and propanolol alone at the same dose. Effluent perfusates and peripheral blood samples were assayed by radioimmunoassay for concentrations of 5-HT, SP, and G. Large amounts of all three humoral agents were found intraluminally during the interdigestive period. The meal resulted in increased circulating levels of 5-HT, SP, and G, while intraluminal concentrations of 5-HT and SP but not G increased following the meal. Both atropine and propanolol pretreatment significantly reduced this response, while alone, these drugs did not affect basal values. We postulate that 5-HT and SP released into the intestinal lumen in response to a meal act as local neurocrine/paracrine modulators. Their release mechanisms appear to be under both cholinergic and adrenergic control.