Despite extensive epidemiological evidence suggesting that Kaposi's sarcoma (KS) has an infectious origin, a specific viral association with KS had not been documented until recently, when two novel DNA fragments were identified in KS lesional tissue from a patient with the acquired immunodeficiency syndrome (AIDS). These fragments belong to a previously unidentified human herpesvirus, called KS-associated herpesvirus (KSHV), or human herpesvirus 8. Although this virus is generally absent from normal control tissues, inflammatory conditions, and a variety of tumors, it is present in most AIDS- as well as non-AIDS-related KS lesions, suggesting that it is not simply an opportunistic infection in human immunodeficiency virus (HIV)-infected patients. Furthermore, this virus is consistently present in a specific type of non-Hodgkin's lymphoma, frequently although not exclusively occurring in patients with AIDS (namely, the primary effusion lymphomas, previously called body cavity-based lymphomas). KSHV is also present in a significant proportion of cases of AIDS- and non-AIDS-related multicentric Castleman's disease. Sequence analysis has led to the identification of genes in the KSHV genome that may have important pathobiological functions, and experimental approaches have been developed to isolate, grow and transmit KSHV in vitro. An understanding of KSHV is important for evaluating its role in the pathogenesis of Kaposi's sarcoma, primary effusion lymphomas, and multicentric Castleman's disease, and to help develop better methods for the prevention and treatment of these diseases.