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Background Much of the evidence that human herpesvirus type 8 (HHV-8) is associated with Kaposi's sarcoma (KS) has come from molecular studies of HHV-8 DNA. Seroepidemiological studies have been hampered by the lack of a reliable assay.Methods The serological data reported here were obtained by means of a mouse monoclonal antibody-enhanced immunofluorescence assay for antibodies to lytic and latent HHV-8 antigens. 1435 single samples of serum (or plasma) from many different disease groups and parts of the world were assayed.Findings All patients with African endemic KS and 96 percent of American patients with AIDS-associated KS were seropositive for lytic antigen, as were 90 percent of American HIV-infected homosexual men; by contrast only 23 percent of HIV-seropositive drug users and 21 percent of HIV-seropositive women were positive for HHV-8 antibody. Factor VIII treatment before 1983 did not increase the risk of HHV-8 infection in patients with haemophilia. In the American general population, about 25 percent of adults (including volunteer blood donors) and 2-8 percent of children had antibodies to HHV-8.Interpretation Our data are consistent with HHV-8 being primarily associated with sexual transmission, but the HHV-8 seropositivity rate in American children suggests that there is a non-sexual route of HHV-8 infection also. On the evidence available so far, the risk of parenteral transmission is low.858-61.