To study the role of pancreatic blood flow and vasoactive substances in the development of acute pancreatitis, we measured portal vein blood levels of bradykinin, prostaglandin E2 (PGE2), histamine, serotonin, and pancreatic enzymes, and with an electromagnetic blood flowmeter we recorded gastroduodenal arterial flow (GDAF), superior mesenteric arterial flow (SMAF), and mean arterial blood pressure for 6 hr in dogs with acute hemorrhagic necrotizing pancreatitis induced by the retrograde injection of autologous bile (0.5 ml/kg) into the pancreatic duct. GDAF and SMAF decreased immediately in the early phase of acute pancreatitis (-17.8 +/- 6.1%** at 10 min and -15.8 +/- 7.1%* at 20 min; *P < 0.05, **P < 0.01); portal bradykinin concentration increased quickly (3.2 +/- 1.2 pM at 0 time, 16.2 +/- 5.2 pM* at 5 min, 30.4 +/- 4.8** pM** at 10 min, and 39.6 +/- 15.1 pM* at 20 min). Portal PGE2 concentration increased gradually after the induction of acute pancreatitis, and differences from the control group were significant at 20, 30, and 180 min (1426 +/- 175 pM at 0 time, 1956 +/- 273 pM* at 20 min, 2148 +/- 265 pM** at 30 min, and 3369 +/- 686 pM* at 180 min). Portal histamine and serotonin concentrations increased somewhat, but not significantly. These findings suggest that the injection of bile into the pancreatic duct causes the pancreas to quickly release a large amount of bradykinin into the portal vein, which immediately reduces the pancreatic blood flow in the early phase, thus accelerating the progress of acute pancreatitis.