Background/Aims: Symptoms of attention deficit hyperactivity disorder (ADHD) have often been associated with early-onset smoking. We hypothesize that reductions in ADHD symptoms due to an intervention have a mediating effect on early-onset smoking. Methods: In a universal, school-based, randomized controlled intervention trial, we examined whether intervention-induced reductions in ADHD symptoms at age 9 mediated the reduced risk of tobacco use onset among these children at age 10 or 11 years. A sample of 477 first-grade boys and girls were randomly assigned to the Good Behavior Game intervention (n = 263), a 2-year (grades 2 and 3) universal classroom-based intervention aimed at reducing disruptive behavior problems, or to a control condition (n = 214). ADHD symptoms were assessed through teacher ratings. Early onset of tobacco use was assessed through self-report. Results: The intervention-induced reductions in ADHD symptoms fully mediated the distal effect of intervention on reductions in early-onset smoking. Conclusions: Our results showed that programs that target ADHD symptoms may protect children from early-onset smoking as well. Further research is needed to examine pathways from ADHD symptoms to tobacco use. Copyright © 2008 S. Karger AG.