OBJECTIVE Despite advances in the treatment of chronic hepatitis C virus (HCV), the disease persists after treatment with interferon and ribavirin in a large percentage of patients and other therapeutic options are lacking. We investigated the efficacy of retreatment with antiviral therapy including amantadine. EXPERIMENTAL DESIGN prospective and open pilot study. PATIENTS Thirty-nine patients with chronic HCV, genotype 1, who were nonresponders to interferon and ribavirin were included. The patients were given repeat treatment with interferon-alpha 2A (9 MU/week), ribavirin (1,000-1,200 mg/day) and amantadine (200 mg/day) for 48 weeks. RESULTS HCV-RNA was undetectable in 5 patients in week 48 (12.8%) and in only 2 patients after 24 weeks of follow-up (5.1% of sustained responses). In patients with basal viremia of < 8 105 U/ml the probability of response at the end of treatment and of sustained response was 26.3 and 10.5%, respectively; in patients with elevated viremias response was 0%. CONCLUSIONS In patients with chronic HCV genotype 1 without response to interferon and ribavirin, triple antiviral therapy with interferon, ribavirin and amantadine is not useful.