Background and Objective: Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) provides remarkable relief of tremor in the limbs contralateral to the side of the brain stimulated. The benefits have been sufficiently dramatic that this is now an accepted clinical treatment of essential as well as other forms of tremor. Despite this clinical benefit, the mechanism of action of DBS remains unknown. In this investigation, we sought to determine the effects of VIM DBS on neuronal function. Methods: The authors used PET measurements of qualitative regional cerebral blood flow in patients with essential tremor to determine the effects of DBS in the left VIM. Each subject had four to six scans with the arms at rest and DBS turned either on or off during alternate scans. Continuous physiologic monitoring revealed no tremor during any of the scans. The PET images from each subject were aligned, averaged, and coregistered to a standard image oriented in stereotactic space. Results: The authors used subtraction image analysis with statistical parametric mapping methods and a restricted volume search to identify a significantly increased flow response at the site of stimulation in thalamus. An exploratory analysis revealed increased flow in ipsilateral supplementary motor area, a region that receives afferents from VIM. Conclusions: The increased blood flow at terminal fields of thalamocortical projections suggests that DBS stimulates and does not inactivate projection neurons in VIM thalamus.