Male-to-female transgender individuals who engage in sex work constitute a group at high risk for HIV infection in the United States. This mixed-methods formative study examined sexual risk among preoperative transgender male-to-female sex workers (N =11) in Boston. More than one third of the participants were HIV-infected and reported a history of sexually transmitted diseases. Participants had a mean of 36 (SD =72) transactional male sex partners in the past 12 months, and a majority reported at least one episode of unprotected anal sex. Qualitative themes included (a) sexual risk, (b) motivations for engaging in sex work, (c) consequences of sex work, (d) social networks (i.e., "trans mothers," who played a pivotal role in initiation into sex work), and (e) potential intervention strategies. Results suggest that interventions with transgender male-to-female sex workers must be at multiple levels and address the psychosocial and environmental contexts in which sexual risk behavior occurs.