Electrical low-frequency stimulation (LFS) of afferents evokes long-term depression (LTD) of nociception. In-vitro studies suggest a sole homosynaptic effect on the conditioned pathway. The present study addresses homotopy of LTD in human nociception and pain. In 30 healthy volunteers nociceptive Aä fibers were electrically stimulated by a concentric electrode. Conditioning noxious LFS (1 Hz, 1200 pulses) was always applied to radial side of right hand dorsum and test stimulation was alternately applied (A) to radial and ulnar side of right hand dorsum or (B) to radial side of right and left hand dorsum. After each test stimulus, volunteers were asked to rate the intensity (0-100). Somatosensory evoked cortical vertexpotentials (SEP) were recorded via EEG. After LFS, SEP amplitude (A: -34.6%; B: 33.6%) and pain rating (A: -44.1%; B: -29.1%) under homotopic test stimulation significantly decreased in comparison to heterotopic test stimulation and control session. The electrophysiological and psychophysical study on synaptic plasticity in healthy man demonstrates homotopic organization of LTD. Due to homotopy of LTD heterotopic test stimulation could serve as an endogenous control in order to investigate effects of repeated LFS for several days.