The aim of this study was to characterize the mechanism of the gastrocolonic response to eating in healthy human volunteers. A bipolar clip electrode recorded spike activity from the distal colon. A rapid increase in colonic spike activity occurred after eating a 1000-cal meal (16.1 +/- 2.8 spike potentials/10 min, p less than 0.001). The intravenous infusion of atropine inhibited the increase in postprandial colonic motility. Intragastric administration of procaine, a local anesthetic also inhibited the gastrocolonic response to eating. After sham feeding a modified 1000-cal meal, there was no increase in the gastrocolonic response. Morphine stimulated colonic spike activity (55.3 +/- 15.1 spike potentials/10 min, p less than 0.001). Naloxone (40 microgram/kg . h) completely inhibited morphine stimulation of the colon. Naloxone also inhibited the postprandial gastrocolonic response, but did not inhibit neostigmine stimulation of colonic motility. These data suggest: (1) the gastrocolonic response is mediated by afferent neural receptors in the gastroduodenal mucosa, (2) there is no cephalic phase in the gastrocolonic response to eating, and (3) efferent cholinergic neurons and opiate receptors are both necessary for the gastrocolonic response.