Generally, it has been known that cholecystokinin (CCK) release into the plasma is under cholinergic control, but secretin release is not. Thus in anesthetized dogs we studied the effect of atropine (50 μg/kg followed by 50 μg/kg/hr) on pancreatic secretion and plasma concentrations of bioactive CCK and immunoreactive secretin in response to intraduodenal perfusion of sodium oleate (1, 3 and 9 mmol/hr). The volume, protein output and bicarbonate output of the secretion were increased by sodium cleats and this oleate-induced secretion was decreased significantly by atropine administration. However the increased plasma CCK and secretin levels by sodium oleate were not changed by atropine. These results indicate that atropine suppressed sodium oleate-induced pancreatic secretion through inhibiting cholinergic mechanism directly rather than decreasing the release of pancreatic secretory hormones. In another set of experiments, bilateral cervical vagi were stimulated electrically to observe the changes of pancreatic secretion and the above two plasma hormone levels in the presence or absence of atropine. In the vagally stimulated dogs, the volume, protein output and bicarbonate output of the pancreatic secretion were increased significantly. Both plasma secretin and CCK were concomitantly released significantly by vagal stimulation. Atropine significantly depressed the pancreatic secretory response as well as the release of these two pancreatic secretory hormones. Therefore, we conclude that in the presence of atropine the depressed pancreatic response to vagal stimulation is at least, in part, due to decreased release of endogenous CCK and secretin. In the vagally stimulated animals, however, the involvement of direct cholinergic influence on pancreatic exocrine gland remains to be answered.