Measurements of biliary lipid secretion rates were performed in 10 patients with radiolucent gallstones before and after 4 wk of administration of chenodeoxycholic acid and ursodeoxycholic acid (1 g/day) in a randomized crossover study. The results of both bile acid feeding periods were similar in many respects: expansion of the bile acid pool, increase in bile acid and phospholipid secretion, reduction in cholesterol output, and decrease in percent saturation of hepatic bile, which was more pronounced with ursodeoxycholic than chenodeoxycholic acid therapy. Despite these similarities, the mechanisms by which these two litholytic bile acids induced these changes were quite different. Ursodeoxycholic acid, in contrast to chenodeoxycholic acid, only partially suppresses bile acid synthesis. During chenodeoxycholic acid feeding, the ratio of phospholipids to bile acids increased from 0.264 to 0.307 (p less than 0.05), indicating an increased coupling of phospholipids by chenodeoxycholic acid, whereas ursodeoxycholic acid did not alter this ratio. The molar ratio of cholesterol to bile acid during the chenodeoxycholic- and ursodeoxycholic-acid periods decreased significantly from 0.073 to 0.058 and 0.041, respectively. However, this ratio during the ursodeoxycholic-acid period was unchanged when the amount of ursodeoxycholic acid was subtracted from total bile acid (0.069), indicating that UDCA has little, if any, effect on the mobilization of hepatic cholesterol into bile.