Human herpesvirus 8 (HHV8) is the etiologic agent of Kaposi's sarcoma (KS), a tumor occurring mainly among elderly men in its endemic and classical forms. The male-to-female ratio of KS in different endemic populations ranges from 3 : 1 to 15 : 1. We investigated the influence of age and gender on anti-HHV8 antibody titers among HHV8-seropositive subjects of an endemic population (1819 villagers with 874 men and 945 women) of African origin living in French Guiana. By using a specific immunofluorescence assay, we found that the overall HHV8 seroprevalence of antibodies against lytic antigens was 11.8%. There was no difference between seroprevalence in males (11.7%) and females (11.8%). Among the 214 HHV8-seropositive subjects, anti-HHV8 antibody titers were found to increase with age (P<.001) and were higher in males than in females (P =.003). The geometric mean of HHV8 antibody titers was 1 : 105 (95% confidence interval [CI] = 1 : 77 to 1 : 144) for males versus 1 : 62 (95% CI = 1 : 47 to 1 : 81) for females. The titers increased from 1 : 59 (95% CI = 1 : 43 to 1 : 80) in males younger than 40 years to 1 : 452 (95% CI = 1 : 244 to 1 : 839) in the oldest male group (aged 50 years and older). Such high antibody titers directed against lytic antigens in males aged 40 years and older parallel the increase of endemic KS incidence in older African men. Our results suggest that the role of gender should also be considered in evaluating the association between anti-HHV8 antibody titers in people aged 40 years and older and the risk of developing KS.