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The authors examined early psychopathology as a predictor of trajectories of drug use from ages 13–18 years. Six years of annual data were analyzed for 506 boys using a mixed effects polynomial growth curve model. They tested whether distinct measures of psychopathology and behavioral problems (i.e., attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, depression, and violence) assessed in early adolescence could prospectively predict level and change in alcohol and marijuana use. Higher levels of all of the types of psychopathology predicted higher levels of alcohol use, and higher levels of attention-deficit/hyperactivity disorder, conduct disorder, and violence predicted higher levels of marijuana use. Only conduct disorder predicted linear growth in alcohol use, and none of the measures predicted growth in marijuana use. The results suggest that drug use prevention programs should target youths with early symptoms of psychopathology.