Egypt has a high prevalence rate of hepatitis C (HCV) infection and as much as 90% is genotype 4. Response to interferon (IFN) varies with viral genotype and degree of fibrosis. Genotype 4 is poorly sensitive to standard IFN and IFN-ribavirin combination. We evaluated pegylated interferon (PEG-IFN)-alpha 2b in our patients. Sixty-one patients with compensated chronic HCV genotype 4 were enrolled in two groups: group A (31 patients) received IFN-alpha 2b 3 MU three times per week and group B (30 patients) received 1.5 mu g/kg PEG-IFN-alpha 2b once weekly. Ribavirin was added to each regimen in a dose of 800-1200 mg based on body weight. Patients were followed up for 24 weeks to assess the sustained response (SR). End-of-treatment response (ETR) was achieved in 11 of 31 patients (35.48%) in group A, and 13 of 30 patients (43.33%) in group B (P < 0.05). Only eight patients in group A and 10 in group (B) achieved a sustained virological response (25.8 and 33.3%, respectively) (P < 0.05). By computing ETR, SR or relapse and pretreatment baseline data (pretreatment, viral load, alanine transaminases, necroinflammatory and hepatic fibrosis), both inter- and intragroup, no significant correlations could be detected. In terms of safety and tolerability, PEG-IFN-alpha 2b and IFN-alpha 2b were comparable. In spite of mild insignificant increase in ETR and SR with the pegylated form, the poor response of genotype 4 in Egypt (genotype 4a) to different forms of IFNs may be related to an intrinsic resistance to the direct antiviral effect of IFN.