Between April 1990 and December 1991, 499 (65%) of 767 patients and 142 (59%) of 239 staff members from 11 chronic hemodialysis centers in different geographic regions of the United States participated in a multicenter prospective cohort study that determined the prevalence and incidence of antibody to hepatitis C virus (anti-HCV) and evaluated their risk factors for HCV infection. Serum samples were tested for anti-HCV by enzyme immunoassay and HCV neutralization assay at baseline and 9 and 18 months later. Collected data included patient and staff demographics, number of years a patient had been on dialysis or staff were employed in the dialysis field, history and dates of blood transfusions, history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV was detected in 52 (10%) of 499 patients and in two (1%) of 142 staff members. Logistic regression analysis revealed that in patients, an anti-HCV-positive test was associated with length of time on dialysis (3 or more years), history of injecting drugs, and history of non-A, non-B hepatitis. Anti-HCV positivity was not associated with history of blood transfusions, race, gender, or age. In patients, the cumulative incidence of HCV infection over an 18-month period was 4.6%. Throughout the 18-month follow-up period, no staff members became anti-HCV positive. The association between anti-HCV positivity and increasing patient years on dialysis may reflect the cumulative risk of exposure to infectious blood in the dialysis environment.(ABSTRACT TRUNCATED AT 250 WORDS)