We performed a clinico-pathological study to determine which pre-treatment factors could predict the response to interferon (IFN) therapy in 55 Japanese patients with chronic hepatitis C. Responses to the IFN therapy were evaluated as sustained response, relapse and non-response by the presence or absence of serum hepatitis C virus (HCV) RNA during the course of treatment and at least 6-months post-treatment. The numbers of sustained response, relapse and non-response were 16 (29.0%), 25 (45.5%) and 14 (25.5%), respectively. Eight out of 16 sustained response cases (50%) showed HCV genotype III. Eight among 10 patients with HCV genotype III (80%) were sustained responders. HCV genotypes were found to be correlated with the response to the IFN therapy (p < 0.0001). None of the histological features, the types of the IFN therapy and other clinical factors showed significant differences. These findings suggest that outcome of the IFN therapy in chronic hepatitis C can be predicted by a virological factor, and that HCV genotype III is a useful predictor of a favorable outcome.