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OBJECTIVE: The authors investigated whether the association between adolescent problem behavior and adult substance use and mental health disorders was general, such that adolescent problem behavior elevates the risk for a variety of adult disorders, or outcome-specific, such that each problem behavior is associated specifically with an increased risk for disorders clinically linked to that behavior (e.g., early alcohol use with adult alcohol abuse). METHOD: A population-based group of 578 male and 674 female twins reported whether they had ever engaged in, and the age of initiation of, five adolescent problem behaviors: smoking, alcohol use, illicit drug use, police trouble, and sexual intercourse. Participants also completed a structured clinical interview at both ages 17 and 20 covering substance use disorders, major depressive disorder, and antisocial personality disorder. Data were analyzed with simple bivariate methods, survival analysis, and structural equation analysis. RESULTS: Each problem behavior was significantly related with each clinical diagnosis. The association was especially marked for those who had engaged in multiple problem behaviors before age 15. Among those with four or more problem behaviors before age 15, the lifetime rates of substance use disorders, antisocial personality disorder, and major depressive disorder exceeded 90%, 90%, and 30% in males and 60%, 35%, and 55% in females, respectively. The association between the clinical diagnoses and adolescent problem behavior was largely accounted for by two highly correlated factors. CONCLUSIONS: Early adolescent problem behavior identifies a subset of youth who are at an especially high and generalized risk for developing adult psychopathology.