Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing comorbid non-bipolar mood disorders. Fluoxetine monotherapy is an established treatment for pediatric mood disorders; however its efficacy in ADHD and comorbid mood disorder is unknown. Therefore, we evaluated 30 children who met DSM-IV criteria for ADHD and comorbid non-bipolar mood disorders in a prospective, 6-12-week open-label, study of fluoxetine monotherapy. Fluoxetine was associated with significant decreases in the severity of depressive symptoms, and also, associated with significant decreases on subscales of inattention/overactivity and aggression/defiant symptoms-47% of participants were much or very much improved without observed adverse effects.