"Peripheral" benzodiazepine receptors (PBRs) are located in the central nervous system and the periphery, are involved in the release of dopamine, and are sensitive to agents active at the dopaminergic system. Because attention-deficit hyperactivity disorder (ADHD) is related to dysregulation of dopaminergic neurotransmission, and because benzodiazepines can potentially aggravate the symptoms of ADHD, we have assessed the possible involvement of PBRs in the pathophysiology and pharmacotherapy of ADHD. [(3)H]PK 11195 was used to label platelet PBRs. Platelet PBRs were measured in eight ADHD boys (aged 9-15 years) before and after 4 weeks of treatment with methylphenidate 10-20 mg/day. ADHD patients before treatment did not differ from age-matched healthy controls in [(3)H]PK 11195 binding values. Four weeks of methylphenidate treatment did not significantly affect platelet PBR density in children with ADHD, despite the beneficial clinical effects. These results do not support the involvement of the PBRs in the pathophysiology of ADHD or in the therapeutic effects of methylphenidate.