While high-frequency stimulation of the subthalamic nucleus (STN-HFS) is highly effective in the treatment of Parkinson's disease (PD), the mechanisms underlying its therapeutic action remain unclear. Here, we report changes of single-neuron pallidal activity during STN-HFS in a parkinsonian patient. STN-HFS increased firing rate in both segments of the pallidum. Neurons displayed time-locked responses to stimulation pulses, with an early excitation followed by inhibition and late excitation. Finally, pallidal neurons fired more regularly during STN-HFS. The time-locked responses and increased firing regularity may override abnormally patterned pallidal activity, and thereby significantly contribute to the clinical efficacy of STN-HFS in PD.