The influence of the vagus on the circulating levels of immunoreactive (IR) motilin was determined. Mongrel dogs (5) were equipped with chronically implanted electrodes in the small intestine to record the myoelectrical activity. The release of IR motilin during fasting, after a meal and during an infusion of insulin was studied before and after truncal vagotomy at the diaphragmatic level. When tested at least 2 wk after the operation, the motility pattern of the small intestine and the secretion of IR motilin remained unaltered by vagal section. Cyclic increases in IR motilin associated with phase III of the interdigestive myoelectric complexes were still observed after vagotomy (maximum levels of IR motilin: 250 .+-. 37 vs. 239 .+-. 19 fmol .cntdot. ml-1, not significant), and they were still abolished by feeding or by insulin. An inhibitory influence can probably be mediated by the vagus since, in normal animals, vagal stimulation by a modified sham feeding (tease feeding or presentation of food) at the beginning of a period of phase III activity promptly interrupted this part of the complex and decreased significantly the release of IR motilin by .apprx. 20%. The release of motilin is not chronically altered by distal vagotomy in dogs.