Subthalamic (STH) neurons with slow EPSPs mediated by an N-methyl-d-aspartate (NMDA) receptor were studied in rat brain slice preparation. When STH neurons were intracellularly recorded with KC1-filled electrodes, stimulation of the internal capsule (IC) evoked a short duration depolarization followed by a slow excitatory postsynaptic potential (EPSP) lasting 100–200 ms. The amplitude of the slow EPSP was increased when the neuron was hyperpolarized by a low intensity current injection but was blocked when it was hyperpolarized with strong current. The slow EPSP was reversibly suppressed by application of 30–50 μM dl-2-amino-5-phosphonovareric acid (APV). STH neurons also were recorded, with potassium methylsulfate filled electrodes, in the slice preparation obtained from rats that received chronic knife cuts of the IC at the level of the entopeduncular nucleus. Stimulation of the IC immediately rostral to the STH evoked a fast EPSP followed by a slow EPSP, and IPSPs were largely eliminated in this preparation. The slow EPSP was augmented in MG-free medium and suppressed by 50 μM APV. These results suggest that NMDA receptor mediating slow EPSPs may regulate activities of STH neurons.