The HIV epidemic in Paraguay is concentrated in groups traditionally considered to be most at-risk. For example, the HIV prevalence is estimated to be 2.6 percent in sex workers (Bautista et al. 2006) and 12 percent in men who have sex with men (MSM) (Bautista et al. 2004). The epidemic is concentrated in urban areas, with the highest prevalence found in the capital city, Asunción, and in the border areas with Brazil and Argentina (Alto Paraná, Itapua, and Amambay departments). Ciudad del Este (CDE), the capital city of the Department of Alto Paraná, is located in the eastern region of Paraguay bordering Brazil and Argentina. This border city is strategically important for HIV because of the high concentration of high-risk populations such as truck drivers, sex workers, and drug users, and the social and economic conditions, such as significant legal and illegal trade, economic inequality, and violence, create the structural conditions for high transmission of HIV and other sexually transmitted infections (STIs). There is also high flow of people between CDE and its Brazilian neighboring city of Foz de Iguaçu, located in the southern region of the country, which is the Brazilian region that has the highest AIDS incidence rate (26.3 cases per 100,000) (Ministerio da Saude 2006). Formative research conducted by Population Council/Brazil, supported by the USAID-funded Horizons Project, found that the populations at greatest risk for HIV and STIs include men who have sex with men (MSM), female and male sex workers, adolescent victims of sexual exploitation, and men in prison. It also found that there was an urgent need for implementation of effective STI and HIV prevention interventions in these populations. To respond to this need, the USAID Mission in Paraguay and Population Council/Brazil, in collaboration with Horizons and National AIDS Program of Paraguay, conducted a study to estimate HIV and syphilis prevalence among female sex workers (FSW) and MSM in CDE; examine knowledge, attitudes, and risk behaviors related to HIV and STIs; and describe the contextual and behavioral factors influencing HIV and STI transmission among MSM and FSWs in CDE. Findings provide guidance to the development of HIV and STI prevention and care interventions and further operations research to test strategies and interventions to reduce the spread of HIV and STIs in these groups. Methods One hundred and sixty FSW and 296 MSM who were living in CDE or a neighboring city who were at least 16 years of age and willing to undergo a syphilis test were recruited in CDE between July and December 2006 through respondent-driven sampling (RDS), a method based on participants recruiting their peers into the study. FSW included women who reported having sex in exchange for money, drugs, or gifts in the past 12 months; MSM included men or transexuals who reported having sex with a man at least once during the past 12 months. Data collection consisted of a HIV-related risk behavior questionnaire and a blood sample for syphilis and HIV testing. The l...