Twenty-three patients with gallstones were treated with two dosage levels of ursodeoxycholic acid, 600 mg/day and 150 mg/day. Two to three months after the treatment, the molar percentage of cholesterol in bile significantly decreased (from 7.4 to 4.5 mole % in the 600 mg group and from 7.6 to 4.0 mole % in the 150 mg group), so that bile became unsaturated in most patients in both treatment groups. However, there was no significant difference between the two groups. Biliary ursodeoxycholate increased in proportion to dose, and the sum of ursodeoxycholic acid plus chenodeoxycholic acid in biliary bile acids was over 70%. The was no significant increase in the proportion of lithocholate in bile. The major fecal bile acid of patients receiving ursodeoxycholic acid was lithocholic acid. Serum bile acid concentration rose slightly after 3 months of ursodeoxycholic acid treatment, and the major circulating bile acid became ursodeoxycholic acid. Ursodeoxycholic acid is well absorbed from intestine, undergoes little biotransformation during hepatic passage, and is 7-dehydroxylated by colonic bacteria. The litholytic activity of ursodeoxycholic acid was demonstrated in two patients receiving 450 mg and 150 mg, respectively, of the bile acid per day.