In this 15-year longitudinal study the authors investigated individual and contextual factors that predispose adolescents from a disadvantaged urban area to drug dependence in adulthood. Adolescents were recruited from schools serving East Harlem in New York City. Of the 838 participants followed to adulthood, 59% were women, 55% were African American, and 45% were Puerto Rican. Self-report data were obtained on externalizing and internalizing problems, substance use, and contextual influences across adolescence and young adulthood. Drug dependence was assessed in adulthood. Multivariate logistic regressions of drug dependence were performed on the whole sample and separately by gender. Each of the domains was associated with adult drug dependence. Although mean gender differences were found, most associations of risk factors with drug dependence did not vary significantly by gender. Treating externalizing and internalizing problems, reducing substance use, and providing coping skills for adverse contextual influences in adolescence and young adulthood may reduce the likelihood of becoming drug dependent in adulthood. (Contains 3 tables.)