One hundred forty-five patients on regular hemodialysis (HD) at our institution were evaluated for the presence of hepatitis C virus (HCV) infection. Forty-three patients (29%) were found to have detectable antibodies to HCV using second-generation enzyme-linked immunosorbent and recombinant immunoblot assays. Forty positive patients (anti-HCV+) and 10 negative patients (anti-HCV-) were tested for direct detection of the HCV genome by the polymerase chain reaction (PCR). Twenty-one anti-HCV+ patients (52%) had detectable RNA HCV in plasma (PCR+). No anti-HCV- patient had viremia. In addition, we compared the 43 anti-HCV+ patients with the 102 anti-HCV- patients for duration of HD, history of blood transfusion, serologic markers of hepatitis B virus, and acute and chronic liver disease. On retrospective univariate analysis, statistically significant associations with anti-HCV+ were duration of HD (P = 0.0001), blood transfusions (P = 0.0005), co-infection with hepatitis B virus (P = 0.01), and acute and chronic liver disease (P = 0.06 and 0.01, respectively). Three significant variables (duration of HD, chronic hepatitis, and blood transfusions) of the multivariate analysis permit the classification of 65% of anti-HCV+ patients and 81% of anti-HCV- patients. In the anti-HCV+ group, when the same parameters were compared in PCR+ or PCR- patients, no statistical difference appeared. These results reveal that 52% of anti-HCV+ HD patients have HCV infection. The clinical consequences of HCV infection in that population are not characterized since no difference has been documented between PCR+ and PCR- results.