The effects of peptide YY (PYY) on cholecystokinin-stimulated gallbladder contraction were investigated in the prairie dog model. Twelve animals underwent laparotomy with catheter placement into the gallbladder and common bile duct (vent). The gallbladder was continuously perfused with [14C]polyethylene glycol-labeled lactated Ringer at 0.03 ml/min, and vent effluent was collected at 2.5-min intervals. All animals received 20 min of intravenous infusion of cholecystokinin octapeptide (CCK-OP), 2.5 ng X kg-1 X min-1, immediately followed by 60-min infusions of either lactated Ringer (LR) or synthetic PYY, 10 or 50 ng X kg-1 X min-1. When LR was infused after CCK-OP, gallbladder filling increased by 15.4 +/- 10.5% with minimal changes in gallbladder pressure. Infusion of PYY10 resulted in a significant increase in gallbladder volume (P less than 0.05) and filling (P less than 0.01) with a significant decrease in intragallbladder pressure (P less than 0.05). Similar findings were noted with PYY50. These data indicate that synthetic PYY significantly augments gallbladder filling after CCK-OP-stimulated gallbladder contraction. These findings, coupled with the observation that PYY inhibits pancreatic secretion, suggest that this peptide may be the "anti-CCK" hormone and may have an important role in regulating biliary activity postprandially.