There is an urgent need for continued innovation in the design of HIV/STI prevention interventions for African American females, a group at high risk for STIs and HIV. In particular, attention to social development and to culture is needed. The present study reports on a group randomized controlled trial of a friendship-based HIV/STI prevention intervention delivered at community-based centers in four San Francisco neighborhoods (n = 2, experimental; n = 2, control). This brief program focuses on youth and their friendship group (N = 264). Program outcomes vary by age at 3-month follow-up, evidencing decreases in risky sex in the oldest group (p < or = .05), decreases in multiple partners in the middle age group (p < or = .05), and increases in HIV testing in the youngest group (p = .05). Findings extend recent work on the efficacy of interventions to reduce sexual risk for racial and ethnic minority youth.