We studied the seroprevalence and transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), among 215 Ugandan children, adolescents and young adults. We measured antibodies to a latent nuclear antigen (LANA) and a lytic cycle protein encoded by open reading frame (orf) 65. Infection with KSHV/HHV8 occurred during early childhood and reached adult levels (approx. 50%) before the age of puberty. In children younger than 12 years of age, antibodies to LANA and the orf65 protein were independently associated with hepatitis B infection (p < 0.005). KSHV/HHV8 infection was not associated with antibodies to hepatitis A virus and hepatitis C virus, nor with the quality of the water supply, household size, previous blood transfusions, number of boy/girl friends or marital status. Antibodies to the orf65 protein, but not LANA, were weakly associated with a history of i.v. injections. Our results show that, in contrast to its sexual mode of transmission among homo/bisexual men and sexually transmitted diseases clinic attendees of Northern Europe and the US, transmission of KSHV in Uganda occurs largely before puberty. Among Ugandan children, KSHV transmission follows a horizontal pattern similar to other herpesviruses, in particular the related gamma herpesvirus, Epstein-Barr virus. Transmission of KSHV may be facilitated by living conditions that also promote infection with hepatitis B virus.