The magnitude and clinical significance of Hepatitis C virus (HCV) infection in dialysis patients is controversial and underestimated. This study was conducted in order to evaluate the correlation between HCV replication and antibody response to HCV in dialysis patients. HCV infection in dialysis patients was evaluated over a period of 3 years and compared to HCV infection in Liver Clinic patients. Sera were collected from 310 dialysis patients and tested for anti-HCV and HCV-RNA. In addition, HCV genotype and HCV viral load were determined in HCV-RNA-positive sera. Anti-HCV was detected in 43 (14%) of the dialysis patients. Of these, 37 (86%) were HCV-RNA-positive. Among the 267 HCV-seronegative dialysis patients, 25 (9%) were found to be HCV-RNA-positive in more than one sample during the study. These patients were characterized by low viral load; at least two orders of magnitude lower than in the group of HCV-seropositives. In contrast, in the Liver Clinic patients, HCV-RNA was found exclusively in HCV-seropositive patients. Comparison of the genotype pattern in the two groups did not reveal a difference. Our results suggest that HCV infection in dialysis units may be underestimated due to cases of low viral load, depending on the method of RNA extraction and sensitivity of the test used. Low viral load might contribute to the lack of humoral immune response seen in some dialysis patients.