OBJECTIVE: To study the effects of subthalamic nucleus (STN) stimulation on motor cortex excitability in Parkinson's disease (PD). METHODS: Fifteen patients were evaluated under off-medication, OFF- and ON-STN conditions, using the UPDRS. We studied the effects of STN stimulation on motor cortex excitability under three conditions (OFF, ON with chronic therapeutic parameters, ON HighV with a voltage set 10% under permanent side effects threshold), using transcranial magnetic stimulation. We measured the central motor conduction time (CMCT), rest and active motor threshold (MT), F-wave persistence and amplitude, silent period (SP), intracortical inhibition and facilitation at 3, 5 and 15 ms interstimulus intervals (ISI). RESULTS: The UPDRS motor score decreased from 44.4+/-14.0 under OFF, to 15.2+/-8.0 under ON-STN condition. The CMCT and MT did not change across STN conditions. The F-wave parameters were within normal range under STN stimulation. STN stimulation lengthened the SP and induced facilitation at 15 ms ISI compared to the OFF-STN condition. CONCLUSION: Therapeutic STN stimulation modulates cortical excitability in PD. High voltage STN stimulation could also act on spinal excitability. SIGNIFICANCE: At the motor cortical level, STN stimulation may have a direct effect on intracortical interneurons, modifying the balance between excitation and inhibition.