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The authors investigated relationships between marijuana and inhalant use and several cultural and demographic factors in Anglo American and Hispanic American adolescents (N = 1,094). Outcome measures assessed lifetime and 30-day marijuana and inhalant use. Predictors and covariates used in logistic regression analyses were region, grade, gender, knowledge, acculturation, familism, and parental monitoring. Hispanic Americans exhibited higher usage across all measures. In this group, high acculturation was associated with low marijuana, but high inhalant, use. Across all participants, positive family relations and parental monitoring were strongly associated with attenuated marijuana use but only among those most knowledgeable about drugs. Familism and monitoring were not associated with diminished usage among the less knowledgeable. For inhalants, monitoring combined with high knowledge or high familism was associated with diminished usage.