Abstract: To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-α therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-α 2α (504 million units in total) was defined as complete and sustained CR→SR, n=12), complete response followed by relapse (CR→Rel, n=17), and no response (NR, n=10), excluding dropouts (n=4). Patients who showed CR→SR had a lower HCV-RNA level (0.438 × 106 eq/ml) compared to CR→Rel (2.452 × 106 eq/ml, p=0.008) and NR (4.882 × 106 eq/ml, p=0.009). A higher proportion of patients with CR→SR had type 2a HCV (67%) compared to the CR→Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR→SR, compared to those with CAH2b (p=0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR→SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-α therapy in Japanese patients with chronic hepatitis C virus infection.