Background. The joint influence of living with the mother in a perceived supportive family may be an important HIV/STD-protective factor among sexually active female adolescents. Methods. Sexually active African American female adolescents (N = 522) completed a self-administered survey and structured interview. Adolescents scoring high on family support and reporting that their mother lived with them were compared with the remaining adolescents in respect to unprotected vaginal sex (past 30 days), sex with a non-steady partner (past 6 months), communication with sex partners, attitudes toward condoms, and perceived ability to negotiate condom use. Logistic regression analyses controlled for the influence of parent-adolescent communication about sex and parental monitoring. Results. Adolescents residing with their mothers in a perceived supportive family were more likely to communicate with their sex partners about sexual risk (OR = 1.53). They were less likely to report sex with a non-steady partner (OR = 0.51) or having unprotected sex with a steady partner (OR = 0.52) or any partner (OR = O.55). Conclusions. Controlled analyses suggest that living with the mother in a perceived supportive family is an important HIV/STD-protective factor among female adolescents. HIV/STD prevention programs for female adolescents that include the mothers may promote positive and lasting effects. © 2001 American Health Foundation and Academic Press.