Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.