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Risk and protective factors that predict substance use were investigated with 318 African American high school dropout youths who completed the 1992 follow-up of the National Educational Longitudinal Study of 1988. A conceptual model linking positive family relationships and religious involvement to youths' substance use and conventional peer affiliations through a positive life orientation was examined with structural equation modeling. Positive life orientation, which included optimism and conventional goals for the future, fully mediated the influence of family relationships on conventional peer affiliations. Religious involvement directly predicted conventional peer affiliations and positive life orientation. Conventional peer affiliations mediated the other variables' influence on substance use.