The need for extrinsic neural input to the upper gut in regulation/control of cyclic interdigestive motility and release of motilin remains a topic of controversy. Our aim was to determine whether extrinsic denervation of the upper gut disrupts cyclic release of motilin in relation to the migrating motor complex. Ten dogs underwent transection of all extrinsic innervation and enteric neural input to the stomach, small intestine, colon, pancreas, and liver while enteric neural continuity within this multivisceral complex was maintained. A cyclic pattern of motility occurred during fasting in all dogs in the small bowel (period = 100 +/- 3 min, mean +/- standard error of the mean) and in 8 of 10 dogs in the stomach (period = 98 +/- 4 min). Gastric cycles were temporally coordinated with small bowel cycles. Plasma motilin concentrations cycled temporally with the motility pattern with the greatest concentrations occurring during gastroduodenal phase III-like activity. Exogenous motilin induced a burst of gastric contractions and a premature migrating motor complex in all dogs. Oral meals disrupted cyclic motility and cyclic changes in plasma motilin. Extrinsic innervation to the upper gut is not necessary for cyclic motor activity, for coordinated cyclic release of motilin, or to initiate a premature migrating motor complex-like response to motilin. Central nervous system input (afferent, efferent) is not necessary for cyclic interdigestive activity or cyclic release of motilin.