After receiving a lithogenic regime for 12 weeks (Phase I), 60 hamsters were allocated to groups of 10 animals. During Phase II, except for one group which remained on the lithogenic regime, all groups were switched to a standard diet and chenic acid 20 mg/kg/day or Zanchol 5, 15 or 25 mg/kg/day or no other therapy. Half the animals in each group were sacrificed at 3 weeks and the remainder at 10 weeks. Gallstones were found in all animals except those receiving chenic acid for 10 weeks. At 3 weeks in Phase II, with chenic acid, the bile acid pool size was not significantly decreased and bile remained saturated despite a 38% lower rate of hepatic synthesis of cholesterol (p less than 0.01), but became unsaturated at 10 weeks at which time the bile acid pool size was increased by 37% (p less than 0.01). The highest at which time the bile acid pool size was increased by 37% (p less than 0.01). The highest dose of Zanchol increased the bile acid pool size by 74% (p less than 0.01) while increasing the hepatic synthesis of file acid by 38% (p less than 0.01). None of the doses of Zanchol, however, significantly changed biliary cholesterol saturation. In conclusion, chenic acid decreased the hepatic synthesis of cholesterol prior to increasing the bile acid pool, unsaturating bile and dissolving gallstones. Zanchol did not affect the biliary cholesterol saturation of dissolve gallstones despite an increase in the synthesis and pool size of the bile acids.