The risk and clearance of GB virus type C (GBV-C)/hepatitis G virus (HGV) infection was investigated in a cohort of homosexual men (n=180; median follow-up time, 7 years). The interaction between GBV-C/HGV RNA and antibodies against the E2 region of the virus, and the clinical impact of chronic GBV-C/HGV infection were studied. GBV-C/HGV RNA was detected by RT-PCR, and E2 antibodies were assessed by an immunoassay. At baseline, 63% of the participants had evidence of previous or current GBV-C/HGV infection. The GBV-C/HGV incidence rate was 2 per 100 person-years (95% confidence interval 0. 9-3.8) and was similar to the HIV incidence. The incidence of GBV-C/HGV infection was significantly higher in those reporting unprotected anal intercourse (3.6 per 100 person-years compared to 0 in the group without such sexual contacts). The occurrence of E2 antibodies was strongly associated with GBV-C/HGV RNA clearance. A loss of E2 antibodies was observed at a rate of 1.5 per 100 person-years. It was higher among HIV-infected individuals. Chronic GBV-C/HGV infection was not associated with clinical or biochemical evidence of liver disease.