Patients with end-stage renal disease (ESRD) appear to be at high risk for GBV-C/HGV infection. This information has been obtained with virological techniques (RT-PCR) but few serological data exist. A prototype enzyme immunoassay has now been developed to detect antibodies against the putative envelope protein (E2) located on the surface of the GBV-C/HGV virion particle. We studied the prevalence of GBV-C/HGV infection, as detected by RT-PCR and anti-E2 GBV-C/HGV antibody, in a cohort of chronic dialysis patients (n=157) and renal transplant (RT) recipients (n=77); as a control group, 136 healthy blood donors were tested. The total prevalence of GBV-C/HGV in ESRD was 23% (54/234). The frequency of GBV-C/HGV viremia was 7.7% (18/234) in ESRD and 4.4% (3/68) among healthy blood donors; the prevalence of anti-E2 GBV-C/HGV was 15% (36/234) and 8.8% (12/136) in ESRD and controls, respectively. No relationship was seen between anti-E2 GBV-C/HGV antibody (or GBV-C/HGV viremia) and age, sex, time on renal replacement therapy, anti-HCV, HBsAg and transfusion requirement. No statistical association was observed between GBV-C/HGV and AST/ALT activity. Two of 54 GBV-C/HGV positive patients (3.7%) had raised ALT but were negative for HBV/HCV. In the majority of patients (35/36, 97%) the presence of anti-E2 GBV-C/HGV antibody was linked with the loss of GBV-C/HGV viremia from serum. In conclusion, GBV-C/HGV infection, as detected by RT-PCR and anti-E2 antibody, was common in ESRD, and the rate of infection was higher than in controls. No association was seen between GBV-C/HGV and various demographic or clinical factors. A small group of GBV-G/HGV positive patients tested negative for HBV/HCV and had raised ALT. In many patients exposed to GBV-C/HGV infection the virus was cleared. The clinical significance of GBV-C/HGV in ESRD remains controversial. Prospective studies with additional serological assays are in progress.