There is considerable interest in S100beta protein as a potential marker that can be used to quantify central nervous system injury. However, increasing appreciation that S100beta may be produced by non-neural tissue (specifically adipocytes), has led to a search for more specific markers of brain injury. Recent interests have focused on a cleaved form of tau protein (c tauP) which is elevated in CSF from patients suffering traumatic brain injury. We have investigated whether levels in peripheral blood are a satisfactory alternative to provide an accessible marker of CNS injury severity. We measured levels of S100beta and c tauP in arterial blood from 20 patients with severe head injury. When compared with normal values S100beta was elevated 10-fold in the first 24 hours and c tauP was elevated at all time points, but showed a reversal of the temporal trend observed with S100beta. Patients with a poor outcome (GOS 1-3) had significantly higher S100beta levels on day one. Plasma c tauP levels did not correlate with outcome following head injury.