Objective: To examine associations between parent-adolescent communication about sex-related topics and the sex-related communication and practices of African American adolescent females with partners, as well as their perceived ability to negotiate safer sex. Design: A theory-guided survey and structured interview were administered to 522 sexually active African American females 14 to 18 years old. Recruitment sites were neighborhoods with high rates of unemployment, substance abuse, violence, and sexually transmitted diseases. Multivariate analyses, controlling for observed covariates, were used to identify the association of less frequent parent-adolescent communication with multiple assessed outcomes. Results: Less frequent parent-adolescent communication (scores below the median) was associated with adolescents' non-use of contraceptives in the past 6 months (adjusted odds ratio [AOR] = 1.7) and non-use of contraceptives during the last 5 sexual encounters (AOR = 1.6). Less communication increased the odds of never using condoms in the past month (AOR = 1.6), during the last 5 sexual encounters (AOR = 1.7), and at last intercourse (AOR = 1.7). Less communication was also associated with less communication between adolescents and their sex partners (AOR = 3.3) and lower self-efficacy to negotiate safer sex (AOR = 1.8). Conclusions: The findings demonstrate the importance of involving parents in human immunodeficiency virus/sexually transmitted disease and pregnancy prevention efforts directed at female adolescents. Pediatricians and other clinicians can play an important role in facilitating parent-adolescent communication about sexual activity.