This paper presents epidemiologic data describing the risk of HIV/AIDS and sexually transmitted diseases for African-American female adolescents relative to their white peers. Diverse cultural, psychosocial, and gender influences affect behavior; these should be considered in the development and implementation of culturally sensitive HIV prevention interventions tailored toward African-American female adolescents. These influences include sex-role socialization issues, the African-American family; issues related to racial identity; communication styles common among African-American youth; normative influences in adolescent heterosexual relationships; and factors affecting feelings of self-efficacy, empowerment, and gender rules in the African-American female adolescent. Strategies for incorporating cultural, psychosocial, and gender influences into the development of HIV risk-reduction interventions are suggested. Culturally specific interventions tailored toward this population may be more effective at motivating the adoption and maintenance of HIV-preventive behaviors.