Our objective was to determine whether motilin increases the frequency of cyclic interdigestive motor activity in the canine proximal stomach. In 4 conscious dogs with autotransplanted proximal gastric pouches and gastrointestinal electrodes, intravenous infusions of motilin (0.6 microgram/kg body wt/hr) increased the frequency of the interdigestive cycles by 30% both in the pouch and in the main gastrointestinal tract. However, the 3-min interval between the end of a cycle in the pouch and the end of a cycle in the duodenum was unchanged by motilin. In control experiments, without motilin infusion, the concentration of endogenous motilin in the plasma during the intense contractile phase of the cycles (overall mean 385 pg/ml) was greater in each dog (P less than 0.01) than the concentration during the quiescent phase (overall mean, 256 pg/ml). The concentration of plasma motilin was also greater in the contractile phase (mean, 717 pg/ml) than in the quiescent phase (mean, 587 pg/ml) during exogenous infusions of motilin in two of three dogs (P less than 0.01). We concluded that motilin increased the frequency of cyclic interdigestive motor activity in the canine proximal stomach and that the increase was not dependent on intact proximal gastric extrinsic innervation.