Using in vivo brain microdialysis, we studied amino acid release in the striatum and cortex of eight rats following permanent middle cerebral artery occlusion. We then processed all brains for histopathologic assessment of the volume of ischemic damage 4 hours after occlusion. Ischemic damage was varied by occlusion of the middle cerebral artery at a point either proximal (n = 4) or distal (n = 4) to the lenticulostriate vessels. Proximal occlusion elevated the dialysate contents of all amino acids. The largest increases occurred for the potentially neurotoxic amino acids aspartate and glutamate and for taurine (800-2,800% of basal efflux). We observed smaller increases for the "metabolic" amino acids (280-580% of basal efflux). Distal occlusion did not affect amino acid efflux in the striatum, and release in the cortex was significantly lower than that following proximal occlusion. We compared release data with acute histopathologic outcome. Proximal occlusion resulted in a large volume of ischemic damage in the cortex and striatum (25-48% of hemispheric volume). A smaller volume of ischemic damage was noted following distal occlusion (0-21% of hemispheric volume). The volume of ischemic damage and the amount of amino acid release were significantly correlated (p less than 0.05).