The treatment of chronic hepatitis C with a standard regimen of therapy with interferon (IFN) alpha for 6 months results in a sustained response (SR) in a minority of patients with high levels of HCV-RNA. The aim of this study was to assess whether a high dose of IFN and IFN beta induction/IFN alpha therapy increase efficacy, and to identify the determinants or predictive factors of SR in patients with IFN resistant chronic hepatitis C. In 99 patients with high levels of HCV-RNA (>1 Meq/ml), we compared the efficacy of IFN beta induction/IFN alpha therapy (n=50) and IFN alpha monotherapy (n=49). HCV-RNA clearence was observed in 22 patients (44%) in IFN beta induction/IFN alpha group and 11 (22.4%) in IFN alpha monotherapy group at 7 days after the start of treatment, there were significant difference between these two groups (P=0.0327); in 26 (52%) and 13 (26.5%) at the end of treatment, there were significant difference between these two groups (P=0.0134); in 9 (18%) and 3 (6.1%) at 6 months after the end of treatment, there was no difference between these two groups (P=0.1212), respectively. SR was observed in 9 (18%) and non-response in 41 (82%) with the IFN beta induction/IFN alpha therapy, and in 3 (6.1%) and 46 (93.9%) with IFN alpha monotherapy, respectively. IFN beta induction/IFN alpha therapy was better than IFN alpha monotherapy by HCV-RNA clearance at 7 days after the start of treatment and at the end of treatment, but there was no significant difference between these two groups at 6 months after the end of treatment. IFN beta induction/IFN alpha therapy was superior to IFN alpha monotherapy in the treatment of chronic hepatitis C, and this therapy may be recommended for patients with high levels of HCV-RNA of chronic hepatitis C.