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 less than or equal to 0.05), decreases in multiple partners in the middle age group (p less than or equal to 0.05), and increases in HIV testing in the youngest group (p = 0.05). Findings extend recent work on the efficacy of interventions to reduce sexual risk for racial and ethnic minority youth. (Contains 1 note, 3 tables, and 1 figure.)