The literature regarding the relationship between adolescent social anxiety and substance use is sparse, and available studies have produced discrepant results. Similarly, negative affectivity is a mood-dispositional dimension that is infrequently considered in studies of substance use. The authors used dispositional structural equation modeling to examine the concurrent relationships of social anxiety and negative affectivity with adolescent substance involvement among 724 students in 1 southern California high school. The final model indicated that increased substance use was associated with having lower grade-point average, being male, being White, having higher levels of negative affectivity, and having lower levels of social anxiety. The findings confirm that negative affectivity is positively related to adolescent substance use, whereas social anxiety appears to be protective against substance involvement.