The aim of the present study was to investigate the effect of motilin at various doses on colonic motility in the interdigestive state. Colonic motility was investigated in five dogs equipped with strain gauge force transducers on the gastric antrum, and on the proximal, middle, and distal colon. Exogenously infused motilin (0.2, 0.5, 1.0 and 2.0 micrograms/kg-hr) dose-dependently increased colonic motility, but the doses of motilin that significantly enhanced colonic motility were 1.0 and 2.0 micrograms/kg-hr in all areas of the colon. Motilin at 0.2 microgram/kg-hr increased the plasma motilin concentration to almost equal to the physiological peak values. The excitatory effect of motilin (2.0 microgram/kg-hr) was abolished by atropine but was not affected by hexamethonium. These results indicate that exogenously infused motilin, which increased plasma motilin concentration to above the physiological peak level, stimulated colonic motility by affecting postsynaptic cholinergic neurons.