Human herpesvirus 8 (HHV-8) infection is common in Africa, but prevalence varies geographically. Studies in Europe and America suggest spread through homosexual contact, but evidence of heterosexual spread is inconsistent. We examined the association between HHV-8 and markers of risky sexual activity in Nigeria. The study subjects included an adult referent population at relatively low risk of HIV infection, patients attending a sexually transmitted disease (STD) clinic, and female commercial sex workers (CSW). Sera were collected between 1991 and 1994 to study the epidemiology of retroviruses and STD in Lagos, Nigeria. Residual samples were tested for HHV-8 antibodies using a K8.1 enzyme immunoassay and for antibodies to syphilis, chancroid, herpes simplex virus 2, HIV-1/2, and HTLV-1. Associations were sought using chi square tests and logistic regression. Overall, HHV-8 prevalence was 26.5% in 2002 study subjects, being higher among CSW and STD patients (31% in each) than in the referent population (19%). HHV-8 prevalence in women was approximately half that in men in both the referent and the STD populations. Increasing age and STD were each associated with HHV-8-seropositivity in men and women, and among women being a CSW was also a risk factor. HHV-8 antibodies were more frequently detected in those with laboratory evidence of STD in each group. Having at least one STD was associated with having HHV-8 antibodies. The higher prevalence of HHV-8 antibody in groups with multiple sexual partners and the association with STD among individuals both support the sexual transmission of HHV-8 in African adults.