The survival of traumatized brain tissue depends on energy substrate delivery and consumption. Excitatory amino acids produce a disturbance of ion homeostasis and thus, increase energy demand. In head-injured patients, massive release of glutamate has been reported, especially in patients with focal contusions. Therefore, we studied the interrelationship between glutamate, glucose and lactate in relation to the type of injury. We investigated 37 severely head-injured patients in which a microdialysis probe was placed next to a focal contusion (n = 14) or together with a ventricular catheter in diffusely injured tissue (n = 23). Within-subject Spearman-rank correlation revealed an overall strong relationship between glutamate and lactate (p < 0.001) and glutamate and glucose (p < 0.01), but not between glucose and lactate (n.s.). The interrelationship was more pronounced in diffusely injured brain (normal CT appearance) compared to the contused tissue. The results demonstrate that glutamate clearly influences the release of lactate following injury, supporting the hypothesis that glutamate "drives" glycolysis in astrocytes. The strong positive correlation between glutamate and glucose might indicate an effect of glutamate upon glucose uptake by cells which differs according to the type of injury.