Efflux of glutamate during cerebral ischemia is known to contribute to brain cell death via processes of excitotoxicity. However, gamma-aminobutyric acid (GABA) is also released during ischemia, and may be protective. In this study, we used in vivo microdialysis to map the efflux of glutamate and GABA from central core and peripheral zones of focal ischemia in mouse brain. We show that the temporal profiles of glutamate and GABA efflux are significantly different in core versus peripheral zones. Calculation of glutamate/GABA ratios demonstrate that, in the core, there is a significant increase above baseline ratios during the first 30 mm of ischemia, which then rapidly renormalizes. In contrast, no significant changes in glutamate/GABA ratios were seen in the ischemic periphery. These data suggest that imbalances in glutamate versus GABA efflux may be an initial trigger of excitotoxic brain damage in the core but not the peripheral zones of focal cerebral ischemia.