To investigate the histological change (change of liver fibrosis) produced by the anti-viral effect of interferon on hepatitis C virus, 40 patients with chronic hepatitis C treated with natural interferon alpha were divided according to the existence of viremia at the end of treatment and 6 months after the end of treatment. The condition of liver fibrosis was scored numerically with a new "hepatic fibrosis score" which is sensitive to more subtle changes than Knodell's fibrosis score. Each portal zone was evaluated separately. End-of-treatment biopsy for the HCV RNA-negative group (negative for HCV RNA at the end of treatment) showed a significant improvement of the "hepatic fibrosis score" as well as the alleviation of necrosis and inflammation. At the end of treatment and 6 months after that, serum procollagen type III peptide levels and serum type IV collagen-7s levels had also decreased significantly in the HCV RNA-negative group. The present study showed that treatment with interferon alpha could alleviate fibrosis in addition to necrosis and inflammation.