To elucidate the role of glutamate in the pathogenesis of altered neuronal vulnerability following sublethal ischemia, we measured the extracellular concentrations of glutamate in the gerbil hippocampus using a microdialysis technique. During and immediately after 3-min forebrain ischemia, the extracellular glutamate level showed a striking increase. However, pretreatment with 2-min ischemia 1 h or 4 days before secondary 3-min ischemia did not alter the amount of glutamate released. The result indicates that cumulative damage and tolerance, which take place after pretreatment with sublethal ischemia, are not induced through modification of the amount of glutamate released during secondary ischemia.