The purpose of the present investigation was to determine the responses of human brain to transcutaneous electric nerve stimulation (TENS) at different frequencies by functional magnetic resonance imaging (fMRI) examinations covering the whole brain of eleven healthy volunteers. Each subject received TENS at acupoints ST36 and SP6 of the left leg at the frequencies of 2 and 100 Hz. Frequency-specific responses were found in motor-related areas, thalamus, limbic system and associated cortex to stimulation of the two frequencies, while the primary somatosensory areas were activated by both. Therefore, it appears that 2 and 100 Hz TENS act through different neuro-pathways in the central nervous system.