The volatile anesthetic agent isoflurane was thought to provide neuroprotection against ischemic damage; however, this effect remains controversial. Using the middle cerebral artery occlusion model and intracerebral microdialysis, the authors monitored the variations of glutamate and taurine concentrations in the extra-cellular space in male rats anesthetized with pentobarbital or isoflurane. Brain injury and edema were evaluated 24 h after ischemia. Isoflurane prevented the ischemia-induced efflux of glutamate and reduced the release of taurine. No difference in the size of the brain lesions was observed with both anesthetics, and isoflurane induced the formation of a bigger brain edema and reduced taurine release. These results suggest that inhibiting glutamate release during ischemia may not be sufficient to improve brain outcome after transient ischemia.