Massively obese patients are at high risk for developing cholesterol gallstones. The objectives of this study were to determine the influence of massive obesity on the cholesterol saturation of bile, and to examine the effect of massive obesity on the ability of chenodeoxycholic acid to decrease biliary cholesterol saturation. Gallbladder bile collected at surgery from massively obese patients was significantly more saturated with cholesterol than bile from non-obese patients who were matched for age, sex and gallstone status (P less than 0.01). Median biliary cholesterol saturation index values for groups of subjects were: no gallstones-not obese (0.83); no gallstones-obese (1.14); gallstones-not obese (1.08); gallstones-obese (1.37). Furthermore, a 5-week course of chenodeoxycholic acid (6 mg/kg/day) was less effective in reducing biliary cholesterol saturation in massively obese patients. The bile of 4 of 10 obese patients remained supersaturated, compared to only one of 10 non-obese patients. These results indicate that biliary cholesterol saturation is raised in massive obesity and that in this condition, the biliary lipid response to chenodeoxycholic acid is diminished. This may explain why obese patients have a relatively poor response to gallstone dissolution therapy with this bile acid.