Correlation between pancreatic exocrine secretion and prostaglandin (PG) output was investigated in the isolated and blood-perfused pancreas in pentobarbital-anesthetized dogs. Intraarterial injections of low doses of secretin (0.03-1 units) caused dose-dependent increases in the secretion of pancreatic juice without affecting the output of PGs. Increased secretion was not modified by indomethacin treatment (5 mg/kg, i.v.). Intra-arterial injections of high doses of secretin (4 and 8 units) stimulated the output of both pancreatic secretin and PGE2 and 6-keto-PGF1 alpha into the blood of the pancreaticoduodenal vein dose-dependently. Increased output of PGs was completely inhibited by the indomethacin treatment, but pancreatic secretion was not inhibited. Total amylase and pancreatic isoamylase activities in the blood from the pancreaticoduodenal vein were increased by the injection of secretin (8 units, i.a.). These results suggest that there is no simple correlation between the ability of secretin to increase the pancreatic secretion and its ability to stimulate PGs synthesis in dog pancreas. Increased output of PGs may be due to the consequence of the acute pancreatitis induced by high doses of secretin.