Microinjections of quisqualic acid were made in the spinal cord to evaluate the excitotoxic effects of this excitatory amino acid agonist on spinal neurons in the rat. Animals were divided into four groups based on post injection survival times of 7-49 days. Injections ranging from 0.3 to 2.0 microL of 8.3, 83, and 125 mM quisqualic acid or normal saline were made in the lower thoracic and upper lumbar spinal cord. At all survival times evaluated unilateral injections of quisqualic acid produced unilateral or bilateral cell death and a prominent inflammatory reaction. In 23/25 animals spinal cavities were also observed. Spinal cord segments at or near quisqualate injection sites contained darkly stained, hypertrophied neuronal profiles, and increased staining for glial fibrillary acidic factor. Immunostaining for glial fibrillary acidic factor was especially intense in areas of neuronal degeneration and in border areas of spinal cavities. The results of this study suggest that the intraspinal injection of quisqualic acid may be an effective method to study the mechanisms of excitatory amino acid neurotoxicity, and the pathogenesis of spinal cavitation following neuronal injury.