We have previously shown that in patients with Parkinson's disease (PD), high-frequency stimulation (HFS) of the subthalamic nucleus (STN) modifies spinal excitability via subcortical reticulospinal routes. To investigate whether STN-HFS also modifies spinal excitability via transcortical routes in PD, 10 patients with PD (9 men, 1 woman; 58.3 +/- 8.3 years) were investigated in the medical OFF-state with or without STN-HFS. The H-reflex of the right soleus muscle was recorded during slight plantar flexion at 20% of maximum force. A conditioning transcranial stimulus was applied at 95% of active motor threshold to the contralateral primary motor leg area (M1) 0-5 ms after eliciting the H-reflex. The same paradigm was applied to 8 healthy individuals (5 men, 3 women; 50.8 +/- 3.0 years). Transcranial magnetic stimulation (TMS) facilitated the H-reflex amplitude in healthy controls. A facilitatory effect of the corticospinal input on the H-reflex was also found in patients with PD, but only with STN-HFS switched on. When STN-HFS was discontinued, the H-reflex was no longer facilitated by the TMS pulse. Accordingly, analysis of variance showed a main effect of stimulation (F = 11.15; P = 0.005), ISI (F = 6.1; P = 0.003), and an interaction between stimulation and group (PD vs. control) (F = 8.9; P = 0.01). STN-HFS restores the normal facilitatory drive of a transcranially evoked motor cortical response to the spinal motoneuron pool. In addition to subcortical routes, STN-DBS also alters spinal excitability via transcortical pathways.