The relation between perceived racial discrimination and substance use was examined in 2 studies that were based on the prototype-willingness model (Gibbons, Gerrard, & Lane, 2003). Study 1, using structural equation modeling, revealed prospective relations between discrimination and use 5 years later in a panel of African American adolescents (M age 10.5 years at Time 1 [T1]) and their parents. For both groups, the relation was mediated by anger and/or hostility. For the adolescents, it was also mediated by behavioral willingness, and it was moderated by supportive parenting. Study 2 was a lab experiment in which a subset of the Study 1 adolescents (M age = 18.5 years) was asked to imagine a discriminatory experience, and then their affect and drug willingness were assessed. As in the survey study, discrimination was associated with more drug willingness, and that relation was again mediated by anger and moderated by supportive parenting. Implications of the results for research and interventions involving reactions to racial discrimination are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)