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Cigarette smoking and nicotine dependence are prevalent among pediatric populations with attention-deficit/hyperactivity disorder (ADHD). We assessed the impact of methylphenidate (MPH) treatment on the smoking behavior of adolescent girls with ADHD/borderline personality disorder (BPD).Twelve female adolescent smokers with ADHD/BPD aged 14 to 19 years were treated with MPH for an 8-week period. The severity of ADHD was assessed by the ADHD Rating Scale (ADHD-RS), whereas the smoking behavior was rated by Fagerstorm Test for Nicotine Dependence (FTND).Significant improvement was detected in ADHD symptoms (ADHD-RS, mean [SD], baseline vs end point: 33.1 [6.8] vs 19.9 [6.8], t = 6.875, df = 11, P = 0.0001). A decline, as assessed by FTND (baseline vs end point: 4.1 [2.6] vs 2.0 [1.9], t = 4.056, df = 11, P = 0.0019), was observed in the severity of nicotine dependence. No significant correlation was found between changes in the ADHD-RS and the FTND after MPH treatment (r = 0.09935, P = 0.7587).Methylphenidate may attenuate smoking behavior in female adolescent smokers with ADHD/BPD.