African-American youths are disproportionately affected by deleterious outcomes associated with risky sexual activity. Arguably, females are at greater risk for these adverse outcomes due to physiological and emotional risk factors, such as depression. The current study examines the relationship between depressive symptomology and sexual risk behavior within a sample of 1,970 innercity, economically disadvantaged African-American adolescents in grades nine and eleven. The findings of this study support a relationship between sexual risk behavior and depressive symptomology for the sample, such that as depressive symptomology increases so does sexual risk behavior. Furthermore, an interaction for gender was found, with depressive symptomology being a stronger predictor of sexual risk behavior for African-American females as compared to African-American males. Implications of these findings for the design of prevention programs specifically tailored to African-American adolescent women are discussed.