High-frequency electrical stimulation through electrodes implanted in the subthalamic nucleus (STN) has been shown to reduce significantly the cardinal symptoms of Parkinson's disease (PD). Despite the success of this treatment, the mechanisms of action of stimulation are poorly understood. To elucidate further the mechanisms of action of deep brain stimulation and its effects on cortical activity, we recorded electroencephalographic potentials from 61 scalp-surface electrodes during low-frequency (5-10 Hz) bipolar stimulation in 11 patients with advanced PD (14 implanted electrodes were tested). In all electrodes tested, stimulation through at least one of the four contacts produced a medium-latency waveform with an average onset of 14 +/- 3 ms and peak at 23 +/- 4 ms. This potential typically increased in magnitude across contacts from ventral to dorsal. Within-subject comparisons of median nerve somatosensory evoked potentials demonstrated that the generator of the medium-latency potential was within the primary sensorimotor cortex or lateral premotor cortex ipsilateral to stimulation. The timing and topography of this potential were consistent with indirect activation of the cortex by excitation of pallido-thalamic axons that traverse the dorsal aspect of the STN. The potential evoked by stimulation through the contact used for optimal clinical effect was highly variable across electrodes and frequently different from the medium-latency potential described above, suggesting that the neuronal elements mediating the medium-latency potential were different from those that mediate the clinical effects.