For nearly every substance--cigarettes, alcohol, marijuana, cocaine, other illicit drugs--and with a variety of definitions of prevalence-- Indian youth show significantly higher rates of use. Until recently, steady increases in drug use by Indian youth have been the general rule, especially for drugs with already high use rates such as marijuana and inhalants. Yet while such high prevalence rates have been consistently and widely reported, little exploration has been undertaken surrounding causal factors involved in decisions to use various substances, or the development of substance abuse within this high-risk group. The National Center for American Indian and Alaska Native Mental Health Research is in a unique position to focus attention on key aspects of substance use and abuse among Indian teens, by building on its current work in the Voices Of Indian Teens project (VOICES). Gathering information on more than 25 developmentally relevant psychosocial constructs from over 2,000 teens, VOICES represent the first longitudinal data set in research with Indian adolescents, with teens followed at six- month periods across three years. The work proposed here will first examine more fully substance use among American Indian teens, including the extent of substance use, differences across important subgroups (e.g., culture group and gender), and patterns of co-morbidity among drug use, alcohol use and psychological symptomatology. Second, it will utilize two psychosocial theoretical frameworks--social learning theory and stress-vulnerability theory--to gain a better understanding of risk factors, change trajectories, and mediating processes underlying substance use. Third, using both social learning and stress-vulnerability theories, it will examine differences between key substance-use groups of adolescents, such as those continuing non-use and those initiating use, and those continuing use and those ceasing use. Only by understanding these issues can we begin to conceptualize, design, and implement successful prevention programs that build on strengths within a culture while addressing theoretically relevant developmental processes underlying various patterns of adolescent use and non-use.