The objective of the present investigation was to determine if baseline glial fibrillary acidic protein (GFAP) expression and the increases in GFAP expression induced by chronic constriction of the sciatic nerve were modified by the specific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Changes in immunohistochemical staining densities of GFAP within the L4 spinal cord were quantified and compared in three groups of animals: (1) nonneuropathic rats, (2) nondrug-treated neuropathic rats, and (3) neuropathic rats treated for 7 days with MK-801. The results indicate that baseline GFAP staining density in naive animals is dependent on NMDA receptor activity and that an ongoing NMDA-dependent signal is, at least in part, responsible for the increase in GFAP observed following peripheral nerve injury.