TO clarify the differential effects on spinal circuitry caused by physicalvsfunctional disconnection from the periphery, we compared changes produced by 3-, 7-or 14-day unilateral sciatic axotomy or tetrodotoxin (TTX) nerve blockade on the abundance or activity of NADPH diaphorase (NDP), cytochrome oxidase (CO) and acid phosphatase (AP) in the spinal cord. Following axotomy, AP and NDP were decreased in the dorsal horn and increased in large cells in the dorsolateral motor nuclei while CO was decreased in ventral horn neuropil. TTX induced a decrease of CO in the ventral horn and NDP in the dorsal horn. This suggests that physicalvsfunctional disconnection causes modulation of distinct intra-cellular pathways in sensory afferents, dorsal horn neurons and motoneurons.