The prevalence of hepatitis C virus (HCV) infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein-1 (MCP-1) is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology & Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naive patients were treated with PEG-IFN-a2b, at a dose of 1801 g/kg subcutaneously every week plus ribavirin at a dose of 1000- 1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a sta- tistically significant difference between patients and control group as regards the quantity of MCP-1 (P < 0.05) (Mann-Whitney test) (P = 0.004). There was a significant difference between responders and nonresponses regarding MCP-1 (P < 0.05), responders showed a higher percentage of cases with initial MCP-1 < 306 (P < 0.05). We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin.