Eating a 1000-kcal mixed meal stimulates an increase in distal colonic motility. Fat is the dietary component which is the major stimulant of colonic spike activity. In this study the colonic spike activity increased similarly after the mixed meal [19.1 +/- 2.4 spike potentials (SP)/30 min] and after the fat meal (19.4 +/- 5.4 SP/30 min). Fat stimulated a concentration-dependent increase in colonic motility only when in contact with the gastroduodenal mucosa. Intravenous administration of Liposyn (100 kcal/hr) did not stimulate an increase in colonic spike activity (3.3 +/- 1.3 SP/30 min) despite greater increase in plasma total fatty acid levels than after the oral ingestion of fat. In contrast both the oral ingestion and the intravenous administration of an amino acid mixture (Aminosyn) inhibited the gastrocolonic response after the 1000-kcal mixed meal. Thus, these studies demonstrate: (1) fat stimulates colonic motility only through direct mucosal contact, and (2) a mixture of amino acid inhibits colonic motility through either mucosal contact or by circulating in the plasma. The exact neurohumoral mechanisms involved in both of these effects is unknown at present.