OBJECTIVE Approximately 60% of patients with chronic hepatitis C treated with a combination of interferon (IFN) alpha-2b and ribavirin are nonresponders. The purpose of the present study was to evaluate the efficacy of treatment with high dose consensus IFN (CIFN) (15 microg/day) in nonresponders. METHODS Patients were administered 15 microg CIFN/day. Treatment was stopped in those whose serum hepatitis C virus (HCV) RNA remained detectable at 12 weeks. Those with undetectable HCV RNA at 12 weeks continued on 15 microg three times per week for a further 36 weeks. RESULTS Twenty-four patients were recruited; six (25%) withdrew before 12 weeks because of side effects. Of the 18 patients who completed 12 weeks of therapy, nine (38%) had undetectable HCV RNA. Seven of nine patients who were HCV RNA-negative at week 12 completed 48 weeks of treatment and two withdrew because of intolerable side effects. At 48 weeks, HCV RNA remained undetectable in three patients. After six months of follow-up off treatment, two patients (8%) continued with no detectable HCV RNA in their sera. CONCLUSIONS High dose induction therapy with CIFN 15 microg/day in prior nonresponders to IFN alpha-2b and ribavirin led to loss of detectable HCV RNA in 50% of patients, but this response was only sustained in 8% of patients on completion of therapy.