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There is continuing concern that pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD) may raise the risk of smoking (the gateway hypothesis). Alternatively, unmedicated people with ADHD may use nicotine to improve attentional and self-regulatory competence (the self-medication hypothesis). From a community sample of 511 adolescents participating in a longitudinal health study, 27 were identified as having ADHD, and 11 of these were receiving pharmacotherapy. Self-report surveys, electronic diaries, and salivary cotinine all indicated that adolescents treated with pharmacotherapy for ADHD smoked less than their untreated counterparts over 2 years of high school. These convergent findings from 3 disparate indicators lend support to the self-medication hypothesis over the gateway hypothesis, although alternative explanations need further study. The findings also suggest that early treatment of psychological and behavioral problems may prevent or delay smoking initiation.