The management of acute hepatitis C virus (HCV) infection after renal transplantation (RT) remains controversial, due to the potential risk of interferon-induced graft dysfunction. There is little experience with combined interferon and ribavirin therapy in this group of patients. We treated four consenting RT recipients who developed acute de novo HCV infection with a combination of interferon-alpha 2b and ribavirin. After 48 weeks' treatment, sustained virologic and biochemical remission were achieved in three patients infected with HCV genotypes 1a, 2, and 6a, respectively. The median time from treatment onset to ALT normalization was 8 weeks. The fourth patient was a non-responder infected with genotype 1b. Dose-dependent hemolysis was the most frequent side-effect. No patient developed allograft dysfunction. Our experience indicates that the judicious use of combined interferon and ribavirin can be considered in selected RT recipients with severe acute hepatitis C infection.