We measured human herpesvirus-8 antibodies (K8.1 and orf73 enzyme immunoassays) in 4166 children, aged 6-17 years, in a U.S. cross-sectional survey. Forty-six were K8.1 seropositive (weighted seroprevalence: 1.1%) and 20 were orf73 seropositive (weighted seroprevalence 0.4%). K8.1 seropositivity was associated with asthma (odds ratio: 6.3; 95% confidence interval: 2.4-16.9) and hay fever (3.5; 1.1-11.0), and there were borderline associations with measures of crowding and low socioeconomic status.