To study the metabolism of ursocholic acid, control subjects were injected with radiolabeled cholic and ursocholic acids before and after 1 wk of 900 mglday oral ursocholic acid. Daily samples of bile were obtained, and biliary bile acids were extracted and purified to determine bile acid kinetics. During ursocholic acid therapy ursocholic acid became the principal bile acid (35% k 3% of total bile acids, mean 2 S.E.M.), and the percentage of biliary cholic and chenodeoxycholic acids decreased (p < 0.05). Cholic acid production fell from 190 k 15 mg/day to 135 2 20 mg/day (p = 0.078). The total bile acid pool was increased twofold (p < 0.05), whereas the deoxycholic acid pool was enlarged from 440 f 170 mg to 1,175 2 90 mg (p < 0.02). As much as 28% of the fed ursocholic acid was excreted in the urine, 85% as the free acid and 15% as the glycine conjugate. During treatment, ursocholic acid became the source for 69% k 11% of biliary deoxycholic acid. The time course of the deoxycholic acid specific activity was modeled as a single pool precursor-product system with a variable time delay for the C-7-dehydroxylation of cholic and ursocholic acids (mean delay 0.86 f 0.11 days, p < 0.001 vs. zero delay). Most of this delay probably arises from a slow process of bacterial C-7dehydroxylation within the colon. These results demonstrate that during ursocholic acid therapy the syn- thesis of primary bile acids continues whereas the formation of secondary bile acids is greatly increased. (HEPATOLOGY 1992; 15:645-650.) Ursocholic acid (UCA, 3a, 7P, 12a-trihydroxy-5Pcholanoic acid) and ursodeoxycholic acid (UDCA) are the 7P-hydroxy epimers of cholic acid (CA) and chenodeoxycholic acid (CDCA), respectively. UDCA is in general use as an oral agent for the dissolution of cholesterol gallstones (11, whereas UCA has been demonstrated to possess similar, but somewhat less effective, litholytic