Infection with hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide. Egypt has the highest prevalence of HCV with more than 90% of infections due to genotype 4. Despite recent success after the introduction of combination therapy with IFN-α and ribavirin, about 60% of patients with HCV genotype 4 fail to respond. Resistance to antiviral therapy remains a serious problem in the management of chronic hepatitis C. In most patients, HCV RNA could be detected in peripheral blood mononuclear cell (PBMC). The aim of this study was to investigate the predictive value of HCV RNA in PBMC of patients with chronic hepatitis C after interferon treatment which may act as the source of reinfection for HCV and lead to persistent infection and recurrence.Seventy patients with chronic hepatitis C were treated with interferon plus ribavirin for 48 weeks, and they all achieved clearance of HCV RNA from serum. At the end of treatment, the HCV RNA in PBMC and serum were detected by Real-Time PCR, and six month later, HCV RNA in serum was monitored to detect sustained virological response.Analysis of the PBMC by real time PCR revealed the presence of detectable HCV RNA in the PBMC of 27% of the patient’s inspite of clearance of serum HCV RNA. During follow up 80 % of the patients who became positive for HCV in serum 6 month after the end of treatment had detectable level of HCV RNA in PBMC at the end of treatment. We conclude that the absence of HCV in the serum of patients with chronic hepatitis C by the end of treatment does not mean that there is no circulating virus. HCV in PBMC can reveal signs of a lack of response to treatment and may be an indicator of the persisting infection.