We administered ursodeoxycholic acid (UDCA) orally, at a daily dose of 600 mg, for 4 months to 36 patients with chronic viral hepatitis C. Another 36 patients with chronic viral hepatitis C, treated with placebo for 4 months, served as controls. None of the patients were alcoholics and none suffering from autoimmune hepatitis. Of the 36 patients in the UDCA-treated group, 13 had high levels of serum gamma-glutamyltranspeptidase (GGT), i.e., exceeding 150 U/l (normal < 50 U/l). Histological examination of liver biopsy specimens obtained from 10 patients in this group before treatment suggested that damage of the interlobular bile ducts was prominent in patients with higher levels of serum GGT. After 1 month of UDCA treatment, significant decreases in the levels of serum GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed (P < 0.05 for GGT and AST), and the decreases continued for the 4-month treatment period. The reduction of GGT levels was the most prominent change in the liver function indices; the percent change in the GGT level was -25.2 +/- 4.4 (mean percent change +/- SE) at 1 month and -38.0 +/- 5.0 at 4 months. A significant correlation was observed between the serum delta GGT level (GGT value before treatment minus value after 3 months of treatment) and the total score for morphological injury of the bile ducts (P < 0.05). These results suggested that UDCA has the potential to reverse hepatocellular damage in patients with chronic viral hepatitis C, in whom high GGT levels may be due, in part, to a damaged interlobular bile duct. UDCA may be useful for the treatment of chronic viral hepatitis C, especially in patients exhibiting a high level of GGT.