Electrical low-frequency stimulation (LFS) of nociceptive afferents evokes long-term depression (LTD) of pain. In-vitro studies suggest a sole homosynaptic effect on the conditioned pathway. The spatial organization of LTD in man is still unclear. Thus, the present study addresses the hypothesis that noxious LFS evokes homotopic LTD in man. In 36 healthy volunteers 86 psychophysical experiments were performed. Painful electrical test stimulation and conditioning LFS (1 Hz, 1200 pulses, 4-fold pain threshold) were applied by a concentric electrode. Electrical stimulation was performed on both dorsal hands (A), on right hand dorsum (B), or on low-back (C). Volunteers rated electrically-evoked pain perception according to a verbal rating scale (0 to 100). (A) Test stimulation was alternately applied to radial sides of right and left hand dorsum. After LFS on right hand dorsum pain rating significantly decreased (-26.8 %, p<0.001) exclusively on homotopic right hand. (B) Test stimulation was alternately applied to radial and ulnar sides of right hand dorsum. After radial site LFS pain rating significantly attenuated (- 44.1 %, p<0.001) exclusively within the same area. (C) Test stimulation was performed within left dermatome T12 on low-back. LFS was applied either within the same receptive field as determined by two-point-discrimination (T12) or remote in dermatome T8. After LFS within dermatome T12 pain rating decreased (-18.8 %, p<0.05) only in T12 but not in T8. Results indicate homotopic organization of LTD in healthy volunteers. Due to large receptive fields in low-back area, even heterotopic LFS within the same receptive field evokes LTD. Thus, data reveal homosynaptic spatial organization of somatosensory LTD in man.