Globus pallidus internus (GPi) deep brain stimulation (DBS) increasingly shows promising efficacy in the treatment of severe primary generalized dystonia. Functional imaging studies have shown previously that dystonia could be related to abnormal cortical activation during voluntary movement. In the present study, the effects of GPi DBS on regional cerebral blood flow (rCBF) during a motor task were studied in patients with primary generalized dystonia. rCBF was measured using H215O and PET in eight control subjects and six patients with dystonia treated with bilateral GPi DBS. Subjects were scanned at rest and while performing joystick movements. Dystonic patients were tested in two conditions: 'OFF' (stimulator bilaterally switched off) and 'ON' (unilateral stimulation). In the 'OFF' condition, compared with rest, motor activation of the most dystonic hand was associated with overactivity in the contralateral dorsolateral prefrontal cortex, gyrus frontalis medialis, superior frontal gyrus (area 10), frontoorbital cortex and thalamus. In the 'ON' condition, GPi DBS contralaterally to the most dystonic hand induced a decrease of the overactivation in the same areas, as well as the putamen. According to the present study, generalized dystonia is associated with prefrontal overactivation which can be reversed by effective GPi DBS.