High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.