AIM: To evaluate the daily high-dose induction therapy with interferon-α2b (IFN-α2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this diffficult-to-treat patient group.METHODS: Seventy patients were enrolled in this study.Treatment was started with 10 MU IFN-α2b daily for 3 wk,followed by IFN-α2b 5 MU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-α2b 3 MU/TIW+1 000-1 200 mg ribavirin/daily).RESULTS: The dose of IFN-α2b or ribavirin was reduced in 16% of patients because of hematologic side effects,and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-of-treatment response (EOT) and 40% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P = 0.049). Furthermore,lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype (SVR 28% vs74%; P= 0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus.CONCLUSION: Daily high-dose induction therapy with interferon-α2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.