This study examined the relationship of social influences to use drugs and competence variables with lifetime poly-drug use for adolescents residing in inner-city regions. The same model was tested separately for boys and girls. Sixth- and seventh-graders (N = 2400) in inner-city schools self-reported substance use, social influences to use drugs (e.g., friends' substance use), and competence skills (i.e., refusal assertiveness, decision-making). Logistic regressions indicated that friends' smoking and drinking habits, and permissive/ambivalent parental attitudes toward respondents' drinking, were associated with poly-drug use. High self-efficacy and more frequent refusal assertiveness were related to less poly-drug use for the overall sample. Ambivalent/permissive attitudes of friends toward the respondents' smoking were related to greater poly-drug use for girls, but not boys. Perceptions of higher prevalence norms for peer smoking and less frequent refusal assertiveness each were associated with more poly-drug use for boys, but not girls. (Contains 1 table.)