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The Guttman-scaled nicotine, alcohol, cannabis and multiple substance use of seventh graders was evaluated in relation to measures of major life stressors, daily hassles, family cohesion, conflict and expressiveness, coping, and anxiety. Major life stressors, family cohesion, and the subjective distress of daily hassles contributed significantly in stepwise regression analyses for nicotine, cannabis, and multiple substance use. For alcohol use, major life stressors and family conflict were significant. In the case of cannabis and multiple substance use, a moderating interaction of family cohesion and life stress was obtained. Students identified as multiple substance users reported high rates of occurrence of a number of life stressors.