The tricyclic antidepressant drug desipramine (DMI) was evaluated in the treatment of young patients with attention deficit disorder with hyperactivity (ADDH) in an unselected sample of 62 clinically referred patients, 43 (69%) of whom previously responded poorly to psychostimulant treatment. The 42 children and 20 adolescents were assigned randomly to receive DMI (N = 31) or placebo (N = 31) for up to 6 weeks in a parallel groups, double-blind study. Clinically and statistically significant differences in behavioral improvement were found for DMI over placebo, at an average (+/- SEM) maximal daily dose of 4.6 +/- 0.2 mg/kg; 68% of DMI-treated patients were considered very much or much improved, compared with only 10% of placebo patients (p less than 0.001). DMI was well tolerated, even at the relatively high doses used. These findings suggest that DMI can be an effective treatment in the management of pediatric patients with ADDH, including patients who failed to respond to stimulants.