The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man.