Gallbladder bile was aspirated and analyzed for content of bile salts, cholesterol, and phospholipids in 97 patients undergoing jejunoileal bypass. Lithogenic indices (LI) (mole % cholesterol in sample/mole % cholesterol at saturation) were correlated with age, sex, lipid levels and hepatic fatty metamorphosis. The overall incidence of gallstones in the group was 43%(N = 121). Cholelithogenesis was unrelated to age, serum lipid concentrations, LI, or hepatic morphology. A significant relationship was noted between cholelithogenesis and female sex (p <.03). The incidence of gallstones was greater in patients weighing more than 270% of ideal body weight and the LI greater in those weighing more than 230%. The mean LI of bile was greater than 1.0 (supersaturated) in all patients except nongallstone forming diabeties. The lithogenic index in diabeties without gallstones was 0.88 ± 0.11, while in nondiabeties without gallstones, the LI was 1.49 ± 0.10 (p < 0.001). These observations indicate that grossly obese patients have an increased incidence of cholelithiasis, probably related to supersaturation of bile with cholesterol. In addition, female patients are especially at risk, while other parameters had little or no detectable influence on cholelithogenesis in this group of patients.