Many persons who have developmental disabilities and challenging behaviors are treated with multiple medications combined with nonpharmacological approaches. However, the comparative effects from pharmacotherapy frequently are not assessed empirically, do not include corollary behavioral measures, and are not evaluated in the long term. The present single-case study incorporated behavioral assessment methodology in an "open label" evaluation of anticonvulsant (clonazepam), beta-blocking (propanolol), and antidepressant (sertraline and clomipramine) medications on severe aggression in a child with autism. Clinically significant reductions in aggressive behavior were attained with the administration of clomipramine and the reductive effects from the medication persisted for 1.7 years. In addition, clomipramine was associated with the elimination of crisis intervention procedures that had been required to manage the child's aggression. These findings add to the clinical literature describing effective treatment of serious behavior disorders in persons with developmental disabilities using antidepressant medication.