We conducted a double-blind placebo-controlled crossover study to assess the efficacy of deprenyl for attention deficit hyperactivity disorder (ADHD) in children and adolescents with comorbid Tourette's syndrome (TS). Twenty-four subjects (21 boys, 3 girls; mean age 12 years) were enrolled at two sites (University of Rochester and Baylor College of Medicine). The design included two 8-week treatment periods separated by a 6-week washout period. The primary outcome measures for ADHD and tic severity were total scores on the DuPaul Attention Deficit Hyperactivity Scale (DADHS) and the Yale Global Tic Severity Scale (YGTSS). Fifteen subjects completed the study. The primary analysis revealed no statistically significant beneficial effect of deprenyl on the DADHS (mean improvement 1.3; 95% CI, -2.7 to 5.3; p = 0.50). Further post-hoc analyses revealed, however, that the effect of deprenyl in the first period was substantial (p = 0.02). There was a marginally statistically significant beneficial effect of deprenyl on the YGTSS total score (p = 0.06). Deprenyl may improve both ADHD and tics in children with TS and warrants further study.