We investigated basal motility and the motor effects of motilin, erythromycin, and prostigmine on segments of rabbit gastrointestinal tract removed from extrinsic neural and vascular pathway and immersed in an oxygenated organ bath. Motility was recorded by means of four strain gauges sutured on the serosal surface of the segment. During basal recording, clusters of duodenal contractions that propagated distally, resembling phase III activity of migrating motor complex, were seen. Motilin (10(-6) M) and erythromycin (10(-6) M) induced a propagated cluster of contractions similar to the phase III recorded during the basal period. Prostigmine (10(-6) M) induced a simultaneous increase in gastric and small intestinal motility. Atropine (10(-5) M) prevented the motor effect of motilin, erythromycin, and prostigmine. Thus, MMCs do not appear to require central input for initiation and propagation. Motilin and erythromycin stimulate MMCs through an enteric cholinergic mechanism; therefore, the previously reported smooth muscle receptors for both substances were not apparent in the ex vivo preparation.