Continuous mechanical and electrical activity recordings of the gastroduodenal junction and duodenum were performed in conscious sheep receiving pharmacologic agents delivered intraduodenally before and after nerve section. Sheep on a normal diet regimen exhibited cyclic periods of maximal activity (phase III of the migrating myoelectric complex) on the duodenum or in-series contractions on the duodenal bulb recurring at a frequency of 13/24 hr and more after nerve section. Among the variety of agents triggering in intact animals premature phases of maximal activity, methysergide, when administered locally, was found to increase the number of complexes to a frequency of 24/24 hr, even when extrinsic nerve supply was removed. The results suggest that in the ovine model the mechanism of cycling of the motor events involved serotonergic myenteric neurons located in the duodenal bulb. The data were consistent with the regulation of the enteric biological clock via 5HT neural receptors mediating inhibition.