Recent studies have detected alarming levels of HIV and other STDs in a unique population: biological males who define themselves as females (termed here as trans women). The proposed study by a new investigator affiliated with the National Development and Research Institutes (NDRI) represents a major epidemiological initiative designed to identify and elucidate behavioral and social risk factors for HIV/STDs in this unique group. Using multiple sampling techniques, 550 trans women between the ages of 19 and 39 will be recruited in the New York City Metropolitan Area and tested for HIV, chlamydia, gonorrhea, syphilis and hepatitis B and C. HIV negative subjects will be followed for three years to determine changes in their risk factors, and HIV/ STD infection/reinfection. The prevalence and yearly incidence of HIV in this population will be determined. In conjunction with the cohort research design, using generalized estimating equations (GEE) and other techniques, suggested risk factors for HIV/STDs among trans women will be systematically tested. Aspects of injection drug use (for psychoactive drugs and female hormones) and high-risk sexual behavior (HRSB) will be evaluated as behavioral modes of HIV/STD transmission. Hypothesized associations among economic hardships (e.g. unemployment) and HIV/STDs are expected to be mediated by HRSB with paying sexual partners (sex work). This reflects the notion of "survival sex," where trans women engage in sex work out of financial necessity. Hypothesized associations among gender identity conflict and HIV/STDs are also expected to be mediated HRSB. This reflects the notion of "validation sex," where trans women seek out sexual relationships in an attempt to legitimate a sense of themselves as females, which is otherwise denied to them. The knowledge about HIV/STD etiology that emerges from this study will directly inform future interventions and prevention aimed at this population.