Continuous stimulation of the globus pallidus (GP) has been shown to be an effective treatment for Parkinson's disease (PD). We used the fact that the implanted quadripolar leads contain electrodes within the GPi and GPe to investigate the clinical effects of acute high-frequency stimulation applied in these nuclei and changes in regional cerebral blood flow (rCBF) as an index of synaptic activity. In five patients treated by chronic GP stimulation, we compared the effects on PD symptoms and the changes in rCBF at rest and during paced right-hand movements, with and without left GPe or GPi stimulation. Although improving contralateral rigidity and akinesia, left GPe stimulation decreased rCBF in the left cerebellum and lateral premotor cortex at rest and significantly increased it in the left primary sensorimotor cortex (SM1) during movement. In contrast, left ventral GPi stimulation, which improved rigidity and worsened akinesia, decreased rCBF in the left SM1, premotor area, anterior cingulum, and supplementary motor area but did not modify the movement-related activation. GPe stimulation seems to result in a reduced activity of motor-related areas and the facilitation of motor cortex activation during movement, the latter component being absent during GPi stimulation, and this may explain the observed worsening of akinesia.