The overall aim of this Core Center of Excellence (CCOE) is to conduct research that will transform etiological models of drug abuse and sexual risk behavior and the prevention programs they inform in general and those for rural African American children, youth, and their families in particular. The need for this transformation is documented by inclusive reviews of drug abuse and sexual risk behavior prevention efforts that reveal mixed and inconsistent results. This inconsistent impact is a major concern that indicates a need for new approaches to etiologic models of drug abuse and sexual risk behavior, particularly greater articulation of the ways in which the interface among genetic, psychosocial, and developmental processes can be used to transform them. To reach this goal we have assembled a team of senior and early career investigators with a successful history of collaboration who have backgrounds in molecular and statistical genetics, genetic epidemiology, public health, human development, and prevention science. This network of investigators will access the Shared Resources Core, a unique combination of data sets, genetic laboratory and specimen repository resources, statistical and bioinformatic services, and data collection and program implementation teams. Data from seven core projects were collected from more than 6,000 African American individuals, approximately 5,000 (83%) of whom live in small towns and rural communities. These data include (a) longitudinal assessments of drug use and abuse and sexual risk behavior phenotypes; (b) genetic data; (c) developmentally appropriate assessments of self-regulatory processes; and (d) multilevel assessments of individual characteristics, social adaptation, parenting/family processes, and neighborhood/community contexts. The organizational and administrative structure of the CCOE will organize and prioritize CCOE scientists' research efforts, providing an integrated process for translating findings into transformations of etiologic models of drug abuse and sexual risk behavior that increase their predictive utility and the efficacy of the prevention progress they inform.