Many family therapies for adolescent drug use include ecological interventions. The purpose of this randomized clinical trial was to establish whether ecological interventions contribute to the impact of family therapy above and beyond the contributions of family process-only interventions. A family-based ecological approach, structural ecosystems therapy (SET), was compared with family process-only condition (FAM) and community services control (CS). One hundred ninety substance-abusing or dependent African American and Hispanic adolescents were randomized to SET, FAM, or CS. Follow-up assessments were conducted at 3, 6, 12, and 18 months postrandomization. SET was significantly more efficacious than FAM and CS in reducing adolescent drug use. However, these improvements were limited to Hispanic adolescents. The study demonstrates the importance of investigating changes in adolescent drug use as a result of treatment condition across more than 1 racial/ethnic group.