Clinical and experimental investigations have suggested that ursodeoxycholic acid (ursodiol) may have cytoprotective or choleretic action and therefore be beneficial in patients with intrahepatic cholestasis or chronic liver disease. In an open-label study, we treated 45 patients with chronic hepatitis with 300 mg of ursodiol three times daily for six months. At four months, gamma-glutamyl transpeptidase (gamma-GTP) and leucine aminopeptidase levels had decreased. SGOT and SGPT levels also decreased significantly. Evaluation of histologic changes has not yet been completed. No significant differences in improvement of liver function tests were found in a comparison with 19 historical controls. We also studied eight patients with primary biliary cirrhosis, treated for more than one and a half years with 600 mg of ursodiol per day. At one month, itching diminished in five patients who had pruritus. ALPase and gamma-GTP levels decreased significantly, and GOT and GPT levels were also reduced. IgM levels did not change, but the titer of antimitochondrial body decreased by half in two patients. Levels of glycoursodeoxycholic acid increased, and in three patients follow-up liver biopsy showed marked improvement. These preliminary results suggest that ursodiol is safe and effective for the treatment of chronic hepatitis and primary biliary cirrhosis, but a large-scale, controlled trial is needed.