Theories of health behavior posit that change is accomplished by modifying factors deemed as mediators. A set of mediators from several theoretical models used in sexual risk reduction programs was assessed among a sample of 522 African American female adolescents. The goal was to determine whether self-esteem was associated with sexually transmitted disease (STD), pregnancy, and the set of theoretical mediators controlling for covariates. Bivariate analyses showed no relationship between self-esteem and STD or pregnancy; multivariate regression analysis revealed a significant relation between self-esteem and the set of mediators. Girls higher in self-esteem were more likely to hold positive condom attitudes, felt more efficacious in negotiating condom use, had more frequent communication with sex partners and parents, perceived fewer barriers to using condoms, and were less fearful of negotiating condom use. Self-esteem should be considered when designing and evaluating sexual risk reduction programs for this population.