Extracellular levels of amino acids in the hippocampal CA1 region of the gerbil were analyzed by a microdialysis-HPLC procedure. Transient forebrain ischemia produced significant increase in aspartate, glutamate, glycine and taurine (760%, 1070%, 190% and 1210%, respectively), and neuronal blockade by perfusion with a lidocaine (4 mM)-containing medium resulted in 67%, 79%, 58% and 59% reduction in the peak values of each amino acid, respectively. On the other hand, an intracerebroventricular administration of lidocaine, 0.8 mumol or more, produced a protective effect against delayed damage of hippocampal CA1 pyramidal cells, which was caused by bilateral carotid artery occlusion for 4 min. The results suggest that lidocaine may protect neurons against ischemic damage, by preventing the ischemia-induced rise of extracellular concentration of excitatory amino acid.