The excitatory neurotransmitters glutamate and aspartate are an important factor in the causation of ischemic brain damage. The concentration of glutamate and aspartate was serially measured in extracellular fluid using in vivo microdialysis after induction of a subdural hematoma or after a sham operation in the rat. Measurements were made in the cortex underlying the hematoma and in the ipsilateral hippocampus, and these findings were correlated with regional cerebral blood flow (CBF), measured autoradiographically 2 hours after hematoma induction. In the severely ischemic cortex underlying the hematoma (mean CBF less than 25 ml/100 gm/min), glutamate and aspartate content increased more than 750% over basal levels. In individual animals the magnitude of glutamate release correlated with the extent of the focal ischemic zone under the hematoma (r = 0.907). Hippocampal glutamate levels rose 339%, yet regional CBF was preserved (114 ml/100 gm/min). This accords with focal hypermetabolism in this model, and may imply a glutamate-mediated "excitotoxic" process after subdural hematoma.