The hypothesis that acid, emptied intermittently from the stomach during fasting, might initiate the duodenal phase of the migrating motor complex was tested in normal human subjects, in addition, the relationship between plasma motilin concentrations and the initiation of migrating motor complexes was examined. Migrating complexes occurred spontaneously in the absence of acid in the duodenal bulb and in the presence of duodenal bulb neutralization with sodium bicarbonate. Thus duodenal bulb acidification is not necessary for initiation of the duodenal phase of the migrating motor complexes. Further-more, cyclical increases in plasma motilin concentrations were not closely correlated with the initiation of the gastric phase of maximal activity of the migrating motor complexes. However, motilin concentrations were decreased significantly following onset of the duodenal phase III. We conclude that neither duodenal acidification nor increases in motilin concentration are necessary to initiate migrating motor complexes in man.