Endogenous opioid peptides may play a role in the genesis of pancreatic damage in acute pancreatitis. The effects of naloxone on the haemodynamic changes in acute pancreatitis were investigated by inducing it in dogs with pancreatic ductal injection of fresh trypsin-bile mixture. In the control group (n = 8), acute pancreatitis was characterized haemodynamically by falls in the maximum positive and negative dP/dt (+/- dP/dt), cardiac output (CO) and cardiac index (CI), and increases in the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) as well as an early reduction of pancreatic blood flow (PBF). In another set of eight dogs (naloxone group), naloxone was given intravenously 10 min after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 h). Compared with untreated dogs, naloxone significantly increased PBF and the +/- dP/dtmax; prevented the significant decreases in CO and CI and increases in PVR and SVR, and reduced significantly the severity of pancreatitis, as assessed by both the histological staging and the mortality rate. These results suggest that naloxone limits the progression of acute pancreatitis from oedematous to haemorrhagic form. It is proposed that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis.