OBJECTIVE Hepatitis C virus (HCV) is prevalent in hemodialysis (HD) patients. These patients experience more side-effects with antiviral treatment. The aim of the present study was to evaluate the efficacy and tolerability of pegylated interferon (PEG-IFN) alpha-2a in chronic hemodialysis patients with chronic hepatitis C. METHODS Twenty-five patients were included into the study. All of the patients were interferon naive, anti-HCV antibodies positive and polymerase chain reaction HCV-RNA positive. Twelve of the patients received PEG-IFN alpha-2a at a dose of 135 microg weekly for 48 weeks (Group 1). The remaining 13 patients who received no specific treatment were used as controls (Group 2). The patients were prospectively followed up for a period of 18 months. Biochemical and virological responses were evaluated at the end of the study period (end-of-treatment response) and 6 months after the completion of therapy (sustained response). RESULTS Virological end-of-treatment response was observed in 10 patients (83.4%) in Group 1 and one patient (7.7%) in Group 2 (P < 0.001). Sustained virological response was observed in nine patients (75%) in Group 1 and one patient (7.7%) in Group 2 (P < 0.001). Alanine aminotransferase (ALT) levels were initially increased in seven patients in Group 1 and normalized in five of these patients at the end of the treatment and sustained biochemical response was 71.4%. In contrast, ALT levels in Group 2 were initially high in five patients and normalized in two of them (40%) at the end of the 48 weeks. Even if most of the patients experienced several side-effects (anemia 75%, fatigue 58.3%, thrombocytopenia 33.3% and leukopenia 33.3%), they did not impose the discontinuation of the treatment. CONCLUSIONS The present study showed that PEG-IFN alpha-2a for 48 weeks is efficacious and well tolerated in hemodialysis patients with HCV.