In response to a central nervous system (CNS) injury, microglia and astrocytes release tumor necrosis factor-alpha (TNF-alpha). This proinflammatory cytokine has been implicated in both neuronal cell death and survival. Here, we show that TNF-alpha is involved in the recovery of neuromotor function following traumatic brain injury. Composite neuroscore and accel rotarod were employed to measure neuromotor function. TNF-alpha-deficient (TNF-alpha(-/-)) mice showed no improvement in their locomotor function up to 28 days following controlled cortical impact brain injury. Although collateral sprouting of the unlesioned corticospinal tract, as assessed by retrograde biotin dextran amine labeling, at the cervical spinal cord was observed following injury in the wild-type mice, such changes were not induced in the TNF-alpha(-/-) mice at 4 weeks after injury. These results provide evidence that TNF-alpha is involved in neuroanatomical plasticity and functional recovery following CNS injury.