Summary: Objective: To test the hypothesis that transdermal nicotine would be efficacious for the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD).Method: This was a double-blind, placebo-controlled, randomized, pilot trial that compared the effects of daily transdermal nicotine (5 mg/16 hrs) to placebo in children and adolescents with ADHD. There was a three-day washout period of all psychotropic medication followed by a one-week treatment period.Results: All 10 subjects enrolled (six males, four females; mean age = 10 years, SEM = 0.8) completed the study. As assessed by the 48-item Conners Parent Rating Scale at endpoint and during the trial, there was a significantly greater reduction in ADHD symptoms on “Learning Problems” and “Hyperactivity” subfactors. Nausea, stomach ache, itching under patch and dizziness were the most frequently reported adverse effects associated with transdermal nicotine.Conclusions: While the results of this study support previous research indicating that nicotinic receptor modulation may be a potentially useful strategy for the treatment of ADHD, therapeutic uses of nicotine are limited due to side effects. Thus, future research should investigate ways of improving the therapeutic index of nicotinic ligands in the treatment of ADHD, such as testing selective nicotinic antagonists alone or in combination with cholinergic agonists.