Background/Aims: To determine the clinical usefulness of a new histological scoring system (grading and staging scores) for predicting a long-term response to interferon therapy and evaluating the efficacy of therapy, we examined biochemical, virological and histological findings during and 1 year after interferon therapy in 109 patients with chronic hepatitis C. Methods: Hepatitis C virus RNA was assayed by reverse transcriptase polymerase chain reaction, hepatitis C virus genotype was determined by reverse transcriptase polymerase chain reaction using type-specific primers, and histological grading and staging scores were determined according to a newer scoring system. Results: The patients were divided into two groups according to the outcome of serum alanine aminotransferase levels and HCV RNA level during and after therapy: 31 long-term responders whose serum aminotransferase level became and remained normal for 1 year after therapy with undetectable HCV RNA in serum and liver and 78 non-responders whose aminotransferase levels did not normalize during therapy or rose again after therapy, Before therapy, the long-term responders had significantly lower viral levels, lower incidence of genotype Ib, and lower staging scores than those of the non-responders, There was no significant difference in grading score between the longterm and non-responders, Multivariate analysis showed that the viral level and genotype are more important predictors of a long-term response than the staging score, Both grading and staging scores decreased significantly at the end of therapy in both the long-term and non-responders, The 1-year follow-up liver biopsy examination in the long-term responders showed that the grading score, but not the staging score, continued to decrease significantly. Conclusions: These findings suggest that: (1) the staging score, but not the grading score, appears to be associated with a long-term response, but the viral level and genotype are more important predictors than the staging score; and (2) both the grading and staging scores decreased significantly with interferon therapy, but the staging score appeared to take longer to improve than the grading score.