The effects of forskolin on the secretion of pancreatic juice and on the intracellular levels of cyclic nucleotides were investigated in preparations of the isolated and blood-perfused dog pancreas. Forskolin (3-100 micrograms) injected intra-arterially caused a dose-dependent increase in the secretion of pancreatic juice. The concentration of bicarbonate in the pancreatic juice induced by forskolin was increased. However, protein concentration was decreased. Forskolin-induced secretion was not modified by pretreatment with atropine, phentolamine, propranolol, cimetidine, sulpiride and verapamil. Forskolin (10-30 micrograms) significantly increased cyclic AMP concentration in the pancreatic tissue before the onset of the pancreatic secretion. On the other hand, cyclic GMP concentration was not influenced significantly throughout 30 min after the administration of forskolin. From these results, it is concluded that forskolin may produce an increase in pancreatic secretion mediated through an increase of intracellular cyclic AMP concentration.