To evaluate the changes of extracelluar amino acid concentrations in the rat cerebral cortex throughout focal ischemia and reperfusion periods, transient middle cerebral artery occlusion (MCAO) combined with an in vivo brain microdialysis technique was applied. During 1 hour of MCAO and subsequent 6 hours of reperfufion, whilst the extracellular glutamate level tended to increase during ischemia, it rapidly returned to the basal level at an early phase of reperfusion. Then, it began to increase again and reached a significantly higher level than the first peak. On the other hand, the extracellular glutamine level became significantly decreased. Aspartate and taurine levels temporarily increased during ischemia and an early phase of reperfusion, and returned to almost the respective basal levels with the lapse of time. Serine, glycine and alanine sbowed no significant change. On histopathological examination, dark and shrunk neurons were observed at an early phase of reperfusion, and these findings gradually became prominent with enlargement of the necrotic lesion. These results suggest that the secondary and persistent increase of the extracellular glutamate level is one of the causal factors in the development of neuronal damage observed in transient focal ischemia brought about by MCAO and subsequent reperfusion.