The hypothesis that pancreatic polypeptide promotes postcontractile gallbladder filling was tested in the prairie dog model. Fifteen animals underwent laparotomy with catheter placement into the gallbladder, distal common bile duct (vent), and femoral vein. The gallbladder was perfused with [14C]polyethylene glycol labeled lactated Ringer's solution at 0.03 ml/min and vent effluent was collected at 2.5-min intervals. All animals received a 20-min intravenous infusion of cholecystokinin-octapeptide, 2.5 ng/kg X min, immediately followed by 60-min infusions of either lactated Ringer's solution or bovine pancreatic polypeptide (PP), 10 or 50 ng/kg X min. Gallbladder emptying and intragallbladder pressure were similar for all three groups after cholecystokinin-octapeptide. When lactated Ringer's was administered after cholecystokinin-octapeptide, gallbladder filling increased by 15.6% with a minimal change in gallbladder pressure. In contrast, infusion of PP10 resulted in a significant (p less than 0.02) increase in gallbladder filling, 64.1% +/- 17.1%, and a significant (p less than 0.05) decrease in intragallbladder pressure, as compared to controls. Similar findings were noted with PP50. These data indicate that exogenous PP significantly increases gallbladder filling after cholecystokinin-induced gallbladder contraction. This enhanced filling results from gallbladder relaxation as manifested by decreased intraluminal pressure. These findings coupled with the observation that serum PP levels remain elevated for up to 6 h after a meal suggest that PP may play a role in the regulation of postprandial gallbladder filling.