Chronic hepatitis C patients with genotype 1 infection, liver cirrhosis, high viral load, or those who have not responded to anti-viral treatment in the past have limited chances of clearing the virus, even with pegylated interferon-ribavirin therapy. In this study we treated such patients with a treatment schedule that combines high dose induction Interferon (IFN), prolonged daily IFN and ribavirin treatment. Twenty-four consecutive patients were included in this study with either genotype 1 infection, cirrhosis, previous non-response to IFN or a combination of these poor-response characteristics. Patients were treated with 10 million units (MU) of IFN daily for 4 weeks followed by 5 MU/day until week 24, 3 MU/day until week 52 and 3 MU thrice weekly until week 76 in combination with 1-1.2 g ribavirin daily. HCV RNA levels were assessed weekly until week 4 and at least once every 3 months thereafter, by a validated assay with a detection limit below 500 copies/mL. Both intention to treat (ITT) and per protocol (PP) analysis showed a high sustained virological response (ITT 67%, PP 80%). A virological response occurred rapidly (before 8 weeks of treatment) in all patients with a sustained response. Relapse after stopping therapy was observed in only 5%. Side-effects were observed frequently, and six patients had to be hospitalized. With this new treatment regimen that combines induction- and prolonged daily interferon treatment with ribavirin it seems possible to eliminate hepatitis C virus in the majority of patients that have an a priori limited chance of sustained response. Further clinical evaluation of intensive interferon and ribavirin combination therapy (now also including PEG-interferon) is recommended in centres that can provide close patient monitoring and experienced hepatological support.