The goal of this study is to define the epidemiology of HIV-1 related Kaposi's sarcoma (KS) as it relates to the putative causal agent, KS herpes virus (KSHV). A proposed historical cohort study nested within the Multicenter AIDS Cohort Study (MACS), a longitudinal prospective study of the natural history of HIV-1 infection in homosexual/ bisexual men, will address these specific aims: (1) determine the prevalence and incidence of KSHV infection in this population; (2) determine the KSHV route of transmission and the concordance of characteristics associated with the virus to risk factors for KS; (3) determine rates and biological markers of progression to KS among KSHV seropositive, HIV-1 infected homosexual men and factors which may modify disease progression; (4) examine the effect of anti-retroviral and anti-herpes treatments on KS disease progression in the presence of KSHV infection; and (5) examine the health effects of KSHV in the absence of HIV-1 and the effect of KSHV on HIV-1 progression independent of its role in KS disease. Behaviors to be examined as risk factors include numbers of male sexual partners and types of sexual activities (e.g., anal/genital intercourse, anal/oral intercourse, genital/oral intercourse) and recreational drug use (e.g., nitrite inhalants). Host characteristics including age, race and immune status will be examined as effect modifiers for viral acquisition and disease progression. The effects of other environmental factors such as geographic location and co-infections will be studied, also. KSHV serological testing will be performed on selected visits for 414 HIV-1 seroconverters with known dates of seroconversion within 1 year and a stratified random sample of 400 HIV-1 seroprevalent and 100 seronegative men. KSHV seroprevalence also will be determined in a sample of injecting drug users from a cohort study with protocols similar as the MACS. Establishing the epidemiology of the KSHV, consistent with principles of causality, will provide direction for developing behavioral and therapeutic interventions against the development of KS and will guide virological and biological investigations determining the pathogenesis of this disease.