One of the late effects of truncal vagotomy is gallbladder dilatation. However, the early physiologic mechanisms responsible for this phenomenon have not been clearly elucidated. Therefore, the hypothesis that truncal vagotomy alters the gallbladder's or cystic duct's response to hormonal stimulation was tested. Adult male prairie dogs underwent either truncal vagotomy and pyloroplasty or sham laparotomy. All animals were then fed a trace-cholesterol (nonlithogenic) diet for 3 months. In acute terminal experiments the gallbladder was aspirated and cannulated with a pressure-monitored perfusion catheter. The common bile duct was cannulated with a drainage catheter. Aspirated gallbladder volume and cystic duct closing pressure were the same in vagotomized and sham animals. Unstimulated intragallbladder pressure and cystic duct outflow resistance were also the same in both groups. However, during an intravenous infusion (10 ng/kg/min) of cholecystokinin-octapeptide (CCK-OP), the maximal intragallbladder pressure increase was greater (P less than 0.01) in vagotomized animals (3.50 +/- 0.41 mm Hg) than in sham animals (1.63 +/- 0.36 mm Hg). Intragallbladder pressure remained significantly higher (P less than 0.05) in vagotomized animals throughout the 30-min infusion of CCK-OP. Despite increased intragallbladder pressure, gallbladder emptying was unaffected by vagotomy. It is concluded that altered gallbladder or cystic duct hormonal response is an early effect of vagotomy that may result in gallbladder dilatation.