Summary. Recent studies have indicated that cytokines can be used as markers for disease progression in hepatitis C virus (HCV)-infected patients, therefore this study was conducted to determine the influence of pegylated IFN vs standard IFN on interleukin-2 receptor (IL-2R), IL-6R, IL-8, TNFR-I, TNFR-II, sFas, and sFas-L in Egyptian patients with chronic hepatitis C genotype 4, as no previous studies have been performed on this genotype. We also aim at establishing a possible relationship between these cytokines and the response to INF to determine whether they can be used as noninvasive markers for the response to INF therapy and as monitors for the outcome of treatment. Thirty-eight patients with chronic HCV hepatitis were investigated for the serum levels of the previously mentioned cytokines in a randomized opened controlled trial (22 patients treated with pegylated IFN and 16 patients treated with standard IFN). Cytokine levels were measured by ELISA at 0, 1 and 12 months of IFN therapy. There was marked increase in the serum levels of IL-2R and IL-6R in nonresponders to pegylated interferon, IL-8, TNFR-I and II were significantly higher in nonresponders to standard interferon but were also high in responders of pegylated interferon. sFas and sFas-L showed high levels among responders to pegylated interferon but the standard interferon was again less effective in this regard. Serum levels of TNFR-II, sFas and sFas-L have the potential to be used as serological markers for response to pegylated IFN therapy, and IL-8 is a predictor for nonresponse. Moreover, TNFR-I and II have the potential to be used as markers of response to standard IFN treatment. The persistent correlation between sFas and TNFR-II may elaborate the possible role of pegylated IFN in the induction of apoptosis as a possible new mechanism of viral clearance during treatment with pegylated interferon treatment.