A longitudinal follow up of 202 hemodialytic patients were conducted to evaluate the incidence of hepatitis C virus (HCV) infection in this high-risk group. A total of 113 patients were found to be seronegative for anti-HCV at the start of this study period. During the average follow-up period of 39 months, 51 patients developed anti-HCV later (group I), while the remaining 62 patients (group II) were seronegative throughout the study period. The results showed that the incidence of HCV seropositivity is 14.6% per year. Longer periods of hemodialysis and younger age of the patient, but not reuse of dialyzer or sex, were correlated with a higher positive rate of anti-HCV. Clinical hepatitis episodes occurred more frequently in group I (56.9%), while persistently normal alanine aminotransferase (ALT) was observed more often in group II (54.8%). There was no significant changes in hepatitis B surface antigen (HBsAg). A total of 41 patients developed hepatitis among the 59 patients who received transfusions, but there was no significant difference between the two groups. We conclude that HCV infection is the main cause of hepatitis in hemodialysis. The longer the patient underwent hemodialysis, the higher the anti-HCV positive rate became, which did not seem to be related to transfusions. Once infected, there is a low disappearance rate of anti-HCV. The exact route of transmission awaits further investigation. © 1993, National Kidney Foundation, Inc.. All rights reserved.