An overwhelming intracranial inflammatory response occurs as a consequence of severe head trauma, leading to cerebral edema and secondary brain injury. Cytokines are important mediators of post-traumatic cerebral inflammation. In the present study, levels of interleukin-12 (IL-12), a pro-inflammatory cytokine which activates cellular immune response mechanisms, were measured by ELISA in 140 matched serum and ventricular cerebrospinal fluid (CSF) samples from ten patients with severe traumatic brain injury. The mean IL-12 CSF levels were significantly elevated in all patients in the course of 14 days after trauma, compared to CSF samples from 15 control patients. Assessment of the IL-12 CSF/serum ratio and of the blood-brain barrier function, using the CSF/serum albumin ratio, suggest that elevated IL-12 CSF levels might be in part derived from intracerebral cytokine synthesis.