The effects of a synthesized phosphodiesterase inhibitor, ZSY-27, on the secretion of pancreatic juice were investigated in dog isolated and blood-perfused pancreas, and compared with those of secretin and dopamine. Intravenous administration of ZSY-27 (0.3-1 mg/kg) elicited increases in pancreatic secretion. Intra-arterial (i.a.) administration of ZSY-27 (0.1-1 mg) also elicited increased secretion. The secretory activity of ZSY-27 (1 mg) was approximately equal to that of 0.1 units of secretin and 2.5 micrograms of dopamine. The concentration of bicarbonate in the pancreatic juice induced by ZSY-27 i.a. was increased, but the protein concentration was not increased significantly. These effects are analogous to those of secretin and dopamine. ZSY-27-induced pancreatic secretion was not modified by pretreatment with phentolamine, propranolol, atropine, sulpiride and cimetidine. Secretin-induced secretion was significantly potentiated by infusion of ZSY-27 (25 micrograms/min) but dopamine-induced one was not. These results suggest that ZSY-27 increases pancreatic secretion acting directly on the ductular cells of the dog pancreas, at least in part, through the increase of intracellular cyclic AMP concentration by inhibiting phosphodiesterase activity.