Traumatic brain injury is associated with release of the excitotoxin glutamate and production of pro-inflammatory cytokines IL-6 and tumor necrosis factor-alpha (TNF-alpha). Following controlled cortical impact injury, cerebrospinal fluid (CSF) glutamate, IL-6, and TNF-alpha concentrations were measured to investigate their relationship to evolving tissue damage. Compared to non-traumatized rats CSF glutamate, IL-6 and TNF-alpha levels were significantly increased by 8 h after trauma (P<0.005). Parallel to increasing brain swelling and contusion CSF glutamate was significantly elevated over time, reaching highest levels by 48 h (33+/-4 microM) while IL-6 and TNF-alpha showed maximum values at 24 h after trauma (42+/-7 and 4.7+/-1 pg/ml) (P<0.005). The observed different temporal profile of CSF glutamate, IL-6, and TNF-alpha following focal traumatic brain injury could be of therapeutic importance.