Objective: Bupropion SR has been shown to be effective for the treatment of nicotine dependence in adults. This open-label pilot study was designed to examine the feasibility and preliminary tolerability of bupropion SR in adolescents with nicotine dependence. Method: Sixteen adolescents aged 12 to 19 years were enrolled in the study. Eleven of the 16 participants also had comorbid attention-deficit/hyperactivity disorder (ADHD). Participants were titrated over 1 week to bupropion SR 150 mg b.i.d. and maintained at this dosage for 6 weeks. Participants also received two brief smoking cessation counseling sessions. Results: Nine participants received at least 4 weeks of medication. There was a significant decrease in the average number of cigarettes smoked (p < .00) and carbon monoxide levels (p = .04) over the course of treatment. Intent-to-treat analysis showed that 31.25% of the adolescents were completely abstinent (5/16) after 4 weeks of taking bupropion SR. Participants' weight did not change significantly during the study (p = .55). There was a no significant change in ADHD symptoms during the study (p = .1). Conclusions: Bupropion SR along with brief counseling may be safe and potentially efficacious for adolescents with nicotine dependence with and without ADHD. Smoking cessation trials in adolescents need to focus on strategies to increase retention for optimal effect. J. Am. Acad. Child Adolesc. Psychiatry, 2004;43(2):199-205.