The role of hepatitis B (HBV) and C (HCV) virus infection in mortality among MHD patients is poorly understood. Recent studies have shown that HCV positivity is associated with significantly higher cardiovascular mortality, especially in dialysis patients younger than 65 years. However, little information is available in European renal registries about mortality among HBV and HCV positive MHD patients. We prospectively followed all patients (prevalents and incidents) attending the dialysis center in the Sicilian region since January 1, 1999, up to December 31, 2000. Those who died for any cause after the starting point were identified and included in the cases population. In all, 698 eligible cases were found. For each case, three controls extracted from the Registry were matched by age at death (within five years) and sex. We calculated the sample size of 698 cases and three controls for each case, assuming the power of the study to be 80%, with an estimated prevalence of exposure among controls of 3.0%. The chi(2) and the t-test were used to evaluate possible differences among cases and controls for the different variables under investigation. The ORs of the association between hepatitis infection and mortality, adjusted for each of the possible confounding factors, was calculated using the Mantel-Haenszel test. The prevalence of Hepatitis C (HCV) was much higher among case compared with controls, both in males (23.4% vs. 17.7 %) and females (25.0% vs. 22.4%). In the multivariate model, the association between HCV and mortality maintained a significant association only among women aged <65 years with an OR of 1.77 (95% CI: 1.12-2.79). We also observed a correlation between increased risk of mortality in hemodialysis and HCV-positive patients with a longer time on dialysis. Our results suggest that HCV positivity among MHD patients is associated with significantly higher mortality in female aged <65 years. For this reason we should be more aggressive in identifying, preventing, and treating HCV infection among patients with end stage renal disease.