Long term total parenteral nutrition (TPN) induces biliary sludge and formation of gallstones. Cholecystectomy is hazardous in these patients because of the underlying medical problems. Therefore, a randomized, double-blind controlled study was designed to test the hypothesis that daily administration of cholecystokinin-octapeptide (CCK-OP) prevents the formation of biliary sludge in humans receiving long term TPN. Adult patients receiving TPN for more than 21 consecutive days were studied. After randomization of 15 patients, the study was concluded because statistical significance was achieved. Eight patients received saline solution (placebo) intravenously and seven received CCK-OP (50 nanograms per kilogram) intravenously over a ten minute period daily. The groups were similar with respect to age, sex, diagnosis, liver function tests, amylase levels, total TPN time and time of study. All of the patients underwent weekly ultrasound studies. Volume and emptying studies of the gallbladder in response to the study drug were performed after one week. None of the patients receiving CCK-OP had sludge whereas five of eight of the patients receiving placebo had sludge (p less than 0.02). The results of emptying studies showed significant contraction of the gallbladder in those in the CCK-OP group but not in the placebo group. These data suggest that CCK-OP given intravenously daily prevents TPN induced stasis and sludge of the gallbladder. We conclude that CCK-OP should be used as routine prophylaxis against biliary sludge and formation of gallstones in patients receiving long term TPN.