High frequency stimulation (HFS) of the subthalamic nucleus (STN) is an effective treatment of idiopathic Parkinson disease (PD). Exactly how HFS works remains unclear. Although HFS of the STN is most effective in improving contralateral motor functions, clinical studies have shown bilateral beneficial effects suggesting that unilateral STN HFS affects both ipsilateral and contralateral basal ganglia networks. In this study we evaluated the effect of STN HFS upon the contralateral STN in 14 PD subjects. The neural recordings were done during stereotaxic neurosurgery for implantation of deep brain stimulation electrodes in the second STN. Neuronal activity of the STN was analyzed before and during two minutes of HFS. There was a significant increase in the multiunit spiking activity of the STN during HFS in the contralateral STN. Our study provides direct electrophysiological evidence that the STN HFS is associated with increased activity of the contralateral STN. These findings suggest that increased STN output underlies therapeutic mechanisms of action of HFS.