The epidemiology of Kaposi's sarcoma (KS) amongst North American and Northern European patients with AIDS suggests that an infectious agent other than HIV is involved in its pathogenesis. Several lines of evidence indicate that human herpesvirus 8 (HHV-8), also termed Kaposi's sarcoma associated herpesvirus, is the sought after agent. DNA of HHV-8 is invariably found in all forms of KS where the virus is present in the KS spindle cell. In contrast, HHV-8 DNA is not regularly detected in most other malignancies. Antibodies against HHV-8 are more frequently found in groups at risk of KS, and HHV-8 seroconversion precedes KS development. Several HHV-8 genes have been identified that exhibit transforming potential in cell culture systems. In addition, the virus encodes and induces several cytokines and angiogenic factors. This is of particular interest as models of KS pathogenesis developed before the discovery of HHV-8 emphasized the importance of inflammatory cytokines. Although the expression pattern of viral genes in KS is not certain yet, it appears likely that the pathogenetic role of HHV-8 in KS may be rather complex and differs from other virus-induced malignancies. 1999 Academic Press.