Patients who receive hyperalimentation undergo prolonged periods of fasting which may alter bile composition and lead to gallbladder stasis, both important factors in gallstone formation. Therefore, we tested the hypothesis that patients who receive long-term TPN are at increased risk for cholelithiasis by performing cholecystosonography on adult patients who had received a minimum of 3 months of intravenous hyperalimentation during 1981. Seventy-one patients whose mean age was 41.9 years, 41 percent of whom were men, met these criteria. Gallstones had been diagnosed in 11 of the 71 patients (15 percent) before the initiation of parenteral nutrition. Twenty-one of the remaining 60 at risk patients (35 percent) were discovered to have cholelithiasis after hyperalimentation was started. The 45 percent prevalence of gallstones in our 71 patients was significantly higher (p less than 0.001) than predicted from autopsy data. In addition, the 49 percent prevalence of cholelithiasis in our 53 patients with ileal disorders was significantly greater (p less than 0.02) than predicted from a study of patients with similarly defined ileal disorders. This analysis strongly suggests that patients who receive long-term TPN are at increased risk for the development of cholelithiasis.