The aim of the present study was to investigate the course of cerebral blood flow (CBF) and metabolism in traumatic brain injury (TBI) patients and to specifically characterize the changes in lactate and glucose indices in the acute post-traumatic period with regard to neurological condition and functional outcome. For this purpose, 55 consecutive TBI patients (mean age 37 +/- 17 years, mean GCS 6.8 +/- 3.2) were prospectively and daily evaluated. Global CBF, cerebral metabolic rates of oxygen (CMRO2), glucose (CMRGlc), and lactate (CMRLct) were calculated using arterial jugular differences. In all patients, CBF was moderately decreased during the first 24 h in comparison with normal subjects although this relative oligemia was more pronounced in patients with poor outcome (p = 0.0007). Both CMRO2 and CMRGlc were significantly depressed and correlated to outcome (p < 0.0001, p = 0.0088). CMRLct analysis revealed positive values (lactate uptake) during the first 48 h, especially in patients with favorable outcome. Both CMRO2 and CMRLct correlated with GCS (p = 0.0001, p = 0.0205). CMRLct levels showed an opposite correlation with CBF in patients with favorable and poor outcome. In the former group, correlation analysis exhibited a negative slope with evidence for increasing lactate uptake associated with lower CBF values (r = -0.1940, p = 0.0242). On the contrary, in patients with adverse outcome, CMRLct values demonstrated a weak though opposite correlation with CBF (r = 0.0942, p = 0.2733). The present data emphasize the clinical significance of monitoring of cerebral blood flow and metabolism in TBI and provide evidence for metabolic coupling between astrocytes and neurons.