The authors have used intracerebral microdialysis to develop a method for routine monitoring of disturbances in brain energy metabolism in patients in the neurosurgical intensive care unit. Microdialysis was conducted for periods ranging from 2.3 to 8.3 days in four patients (three with severe head injuries and one with severe subarachnoid hemorrhage). Altogether, 4447 chemical analyses from 587 dialysis samples were carried out. Concentrations of the energy-related metabolites lactate, pyruvate, and hypoxanthine were measured, and the lactate:pyruvate ratio was calculated. In addition, the acids glutamate, aspartate, taurine, glutamine, asparagine, and glycine were measured in one patient. The microdialysis data were matched with various clinical events, including intracranial hypertension and therapeutic interventions such as initiation or withdrawal of barbiturates and cerebrospinal fluid drainage. The present study shows that microdialysis can be used for long-term measurement of extracellular fluid (ECF) energy-related metabolites and amino acids in the frontal cortex of neurosurgical patients in a clinical setting. Fluctuations of the measured ECF energy-related substances corresponded to various clinical events presumably involving hypoxia/ischemia. The authors found a 25-fold increase in ECF glutamate, aspartate, and taurine under conditions of energy perturbation, as indicated by high levels of the lactate:pyruvate ratio, lactate, and hypoxanthine. The use of long-term intracerebral microdialysis in patients opens a new field of clinical research, with many possibilities for improving insight into intracranial dynamics in acute cerebral conditions.