Background & Aims: Detection of hepatitis C virus RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in the absence of HCV RNA in serum, designated as ‘occult HCV infection', has been a matter of controversy in the recent years. Occult hepatitis C virus (HCV) infection has not been investigated in haemodialysis patients. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) patients in a single heamodialysis center at Al-Taif, KSA. Methods: We enrolled 84 CHD patients, whose sera are negative for HCV markers. HCV RNA was tested in PBMC using a sensitive commercial real time assay. In this study, real-time PCR was used to test for the presence of genomic HCV-RNA in peripheral blood mononuclear cells of all of these patients. For comparison, 20 patients on HD with evidence of chronic hepatitis C virus infection were included as a control group. Results: In CHD patients, occult HCV infection, determined by the presence of genomic HCV-RNA in peripheral blood mononuclear cells (PBMNCs), was found in 13.4 % of the patients; 83 % of these patients had ongoing HCV replication, indicated by the presence of HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on heamodialysis and had significantly higher mean alanine aminotransferase levels during the 3 months before study entry. Compared to CHCV patients, those with occult HCV have less elevated bilirubin, AST and ALT. Conclusions: The prevalence of occult HCV infection was moderate in our CHD patients, and it did not appear to be clinically relevant. Further studies in other geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups. Abbreviations HCV, Hepatitis C Virus ; antibody against HCV; PBMC, peripheral blood mononuclear cells; rRT-PCR, real time reverse transcriptase polymerase chain reaction; CHD, chronic hemodialysis.