Amantadine has been proved to be beneficial in Parkinson's disease. Although it is still uncertain which neurochemical events are modified at therapeutic doses, an increase in dopaminergic tone secondary to NMDA receptor blockade and a direct inhibition of the glutamatergic overactivity have been suggested to be involved in its clinical effects. The aim of this study was to evaluate the effects of amantadine on the dopaminergic system by measuring the in vivo binding of [11-C]raclopride to D2 dopamine receptors in the basal ganglia of 6 patients with idiopathic Parkinson's disease. Each patient underwent a PET study, before and after 14 days of treatment with amantadine (200 mg/day). Repeated treatment with therapeutic doses of amantadine induced a moderate increase in the in vivo binding of [11C]raclopride in the putamen of PD patients. This observation indicates that in PD patients, 200 mg/day amantadine does not produce an increase in extracellular levels of dopamine sufficiently to inhibit raclopride binding or that, if present, is it masked by a concurrent increase in receptor availability, as recently reported in rat striatum.