Substance P was located in the spinal cord of rats by immunocytochemistry. Section and ligation of the sciatic nerve produced a depleted area low in substance P in the medial two-thirds of laminae 1 and 2 of segments L4 and 5. The time of depletion began about 5 days after the nerve had been cut and substance P reached a steady minimum by about 9 days and remained depleted for the entire period examined, 31 days. Crush lesions of the sciatic nerve failed to produce the marked and rapid changes of spinal cord substance P observed after section and ligation.