To assess the prevalence of sludge formation and lithiasis during total parenteral nutrition, serial biliary ultrasonographic studies were performed during and after i.v. nutrition periods in 23 selected adult gastroenterological patients. All patients were free of hepatobiliary disease before i.v. nutrition. Initial sonograms of 19 patients taken at the 12th day +/- 2 days (mean +/- SEM) of i.v. nutrition were normal. Initial studies for the 4 remaining patients, which were performed on the 39th day +/- 10 days of i.v. therapy (p less than 0.001), showed gallbladder sludge but did not demonstrate lithiasis. Serial ultrasonographic studies indicated that the percentage of sludge-positive patients during parenteral nutrition increased from 6% during the first 3 wk to 50% between the fourth and the sixth weeks and reached 100% in patients receiving i.v. nutritional therapy for greater than 6 wk. Gallstone formation was demonstrated in 6 of 14 sludge-forming patients but was not observed in patients who were sludge-negative. Three of the 6 stone-forming patients underwent cholecystectomy because of complications secondary to cholelithiasis after a mean 43-day course of parenteral nutrition. Analysis of bile from these patients revealed thick bile-containing cholesterol crystals and small stones of mixed bilirubin-cholesterol type. Ultrasonographic studies were obtained for sludge-positive patients after the parenteral nutrition period. Sludge positivity decreased from 88% during the first 3 wk of oral refeeding to 0% by the end of the fourth week. This study, therefore, strongly suggests that bowel rest and bile stasis during parenteral nutrition lead to production of sludge, which can result in eventual gallstone formation. Consequently, during parenteral nutrition exceeding 1 mo, gallbladder stasis should be palliated to prevent cholelithiasis formation.