Myoelectric activity induced by a synthetic analogue of the duodenal polypeptide motilin, was studied in isolated vascular-perfused canine duodenum and stomach, and in conscious dogs with serosal electrodes implanted in the stomach and the small intestine. In the isolated preparation, the duodenum was found to be four times as sensitive as the antrum to the polypeptide, showing a dose-dependent increase in spike activity within two minutes after administration of the polypeptide. By contrast, in the conscious fasted animal, the only response to motilin, above a threshold dose, was the interpolation of a premature migrating myoelectric complex in the spontaneous interdigestive sequence, appearing fifteen to twenty minutes after the start of infusion. Since the essential difference between the ex vivo and the intact intestine was the preservation of efferent and afferent nervous connections in the latter, it seems that in the conscious animal, the response to exogenous motilin is modulated by the innervation of the intestine, or, alternatively, motilin interacts with the centre controlling the pattern of motor activity in the small intestine rather than directly with smooth muscle. The latter hypothesis is supported by the observation that motilin had no effect on the motor activity of the small intestine during the infusion of pentagastrin which abolishes spontaneous migrating myoelectric complexes.