In this exploratory study the authors examined the social contexts of American Indian youths' encounters with drug offers and their relationship to substance use. Using an inventory of drug use-related problem situations developed specifically for American Indian youth, questionnaires were completed by 71 American Indian youth at public middle schools in a Southwest metropolitan area. Regression analyses highlight the importance of situational and relational contexts in understanding substance use among the youth in this sample. Exposure to drug offers through parents, other adults, cousins, friends and other peers was associated with different types of substance use. Exposure through parents was particularly salient in predicting the drug use of female respondents. The study underscores the need for development of culturally grounded prevention programs in schools, reservations, and nonreservation communities.