Employing immunohistochemical staining for FOS protein, which is the expression product of c-fos proto-oncogene, the role of substance P receptor (SPR) in noxious information transmission at peripheral terminals of the dorsal root ganglion cells was investigated by means of a selective SPR antagonist L668, 169 and agonist Sar-SP. Unilateral injection of L668, 169 (10(-4) mol/L) into the plantar of hindpaw 10 min before injection of 4% formalin, the number of FOS-like immunoreactive (LI) neurons in the superficial laminae of dorsal horn was significantly decreased, but the changes were not obvious in the deeper laminae. Smaller doses of L668, 169 (10(-5), 10(-6) mol/L) were almost ineffective on FOS-LI neurons in both the superficial and the deeper laminae. However, Sar-SP (10(-4) mol/L) or formalin did result in the expression of c-fos gene in the superficial laminae of the dorsal horn. These results indicated that SP might contribute to the transmission of nociceptive information and induce noxious sensation, at least in part by activating SPR in peripheral terminals of the dorsal root ganglion cells.