Supramaximal stimulation of the rat pancreas in vivo with caerulein elicits a sharp decline in pancreatic juice volume and protein outputs and initiates acute edematous pancreatitis within 30 min. Because of the similar effects of caerulein and bombesin on pancreatic exocrine function, we examined in unconscious rats (a) the effects of a continuous, 4-h intravenous infusion of varying doses (0.2-40.0 nmol/kg/h) of bombesin on pancreatic juice volume and protein output, and (b) whether supramaximal doses of bombesin produce acute edematous pancreatitis. A maximal, fivefold and 17-fold rise in pancreatic juice volume and protein output was achieved with intravenous doses of 1.0 and 4.0 nmol of bombesin/kg/h, respectively. Pancreas weights in rats infused with bombesin as high as 40.0 nmol/kg/h were not significantly different from control animal values (no bombesin infusion) and serum amylase concentrations were only moderately (twofold) elevated over control values in rats i.v. infused with 4.0-40.0 nmol of bombesin/kg/h. The pancreas in rats treated with the highest dose of bombesin (40.0 nmol/kg/h) revealed sparsely scattered microvacuoles in a few acinar cells and minor evidence of interacinar edema. It is concluded that supramaximal stimulation of the rat pancreas in vivo with bombesin fails to elicit acute edematous pancreatitis and appears to be related to the ability of bombesin, in contrast to supramaximal doses of caerulein, to continuously stimulate maximal pancreatic juice secretion.