We investigated a hormonal mechanism involved with cyclic pancreatic secretion in interdigestive state in four dogs prepared with gastric and modified Herrera's pancreatic cannulas and four dogs prepared with gastric and Thomas' duodenal cannulas. Cholecystokinin-pancreozymin (CCK-PZ), secretin, pancreatic polypeptide (PP), and motilin were considered as candidate hormones that might be involved in the mechanism. Radioimmunoassays of the four hormones in serial plasma samples showed cyclic increases in only two hormones including motilin and PP, which coincided with the cyclic increase in pancreatic secretion. However, only motilin given intravenously produced a cyclic pancreatic secretion similar to spontaneous cyclic pancreatic secretion in interdigestive state. Although the magnitude of peak pancreatic secretion was not altered during intravenous infusion of motilin in doses of 0.06 microgram X kg-1 X h-1 or 0.06 microgram/kg, the peak secretion occurred more frequently than that during the control interdigestive state. Atropine administered intravenously abolished the cyclic increases in both plasma motilin concentration and pancreatic secretion. Exogenous secretin, CCK-PZ8 and PP failed to produce cyclic pancreatic secretion. To further elucidate the mechanism involved, the effect of intravenous infusion of a rabbit anti-CCK-PZ or antimotilin serum on the cyclic pancreatic secretion was studied. The antimotilin serum completely blocked the pancreatic secretory cycles in two dogs so studied, whereas rabbit anti-CCK-PZ serum did not influence the pancreatic cycle in two dogs. We conclude that circulating motilin plays an important role on the development of cyclic increase in the pancreatic secretion in two dogs so studied.(ABSTRACT TRUNCATED AT 250 WORDS)