The role of tumor necrosis factor-alpha (TNF-alpha) after spinal cord injury (SCI) is well characterized in the cord, but the impact of this inflammatory process on supraspinal levels is unknown. This study examines TNF-alpha mRNA and protein levels in the brains and spinal cords of mice after SCI. Mice received intraspinal injections of quisqualic acid (QUIS) to create an excitotoxic injury that is known to result in pain behaviors. An ELISA determined serum levels of TNF-alpha, whereas real-time PCR and Western blot analysis were used to determine mRNA and protein levels, respectively, at 3, 6, 12, 24, 48, 72 h, or 14 d postinjury. No difference existed in serum TNF-alpha levels between sham- and QUIS-injected animals. TNF-alpha mRNA in the cord was increased at 3, 6, 12, and 24 h in QUIS-injected animals relative to shams. TNF-alpha protein was elevated at 12 and 48 h postinjury. TNF-alpha mRNA levels in the brain were elevated at 12 and 24 h, with elevated protein levels at 6 h. Animals that developed pain behaviors had increased levels of TNF-alpha mRNA in the brain. Excitotoxic SCI results in altered TNF-alpha mRNA and protein levels in the cords and brains of mice within 6 h of injury. These changes likely contribute to the pathogenesis of injury within the cord. The role of TNF-alpha in the brain postinjury has not been defined but might contribute to the development of pain post-SCI.