A statistically significant elevation was observed in serum and CSF neuron-specific enolase (NSE) levels in patients with major head injury, relative to control individuals. No correlation was noted between serum NSE and either APACHE II, Injury Severity Score (ISS), Glasgow Outcome Score (GOS) or Glasgow Coma Scale (GCS). A significant correlation was noted between CSF NSE levels and GCS, but not between CSF NSE and APACHE II, ISS or GOS. Of the patients with major head injury, 100% had NSE CSF levels above the normal level, while 47% had elevated serum NSE levels. In nine patients with major head injury, changes in CSF levels reflected changes in serum NSE levels. In all nine patients, serum NSE decreased to reach normal values, regardless of the outcome as predicted by the GOS. Therefore, while NSE would appear to be a marker of neuronal cell damage, other markers are also essential.