We evaluated the efficacy of high dose interferon therapy in 122 patients with chronic hepatitis C between 1992 and 1995. They received 612 to 836 mega-units (MU) of recombinant interferon alpha-2b as a total dose during a 6-month treatment in our hospital. Fifty one patients (41.8%) achieved complete response (CR) which was defined as persistent normalization of serum aminotransferase levels and disappearance of serum HCV-RNA for more than 6 months after the end of interferon administration. However, there were no CR in patients with genotype II and in those with serum HCV-RNA levels above 1.5 Meq/ml, quantified by branched DNA probe assay. The rate of CR was not increased even if a total dose of IFN administration was increased from 612 MU to 836 MU. These results indicate that some new regimen of interferon therapy is necessary for these cases with high titer of serum HCV-RNA and genotype II to increase the rate of CR.