Cochlear compound action potentials (CAPS) and glutamate efflux in the perilymph before, during and after transient cochlear ischemia were studied in the gerbil to reveal the mechanisms of ischemia-induced inner ear damage. Cochlear ischemia was created by occluding the bilateral vertebral arteries for 5 minutes, since the posterior cerebral communicating arteries are lacking and the labyrinthine arteries are solely nourished by the vertebral arteries in the gerbil. Occlusion of the vertebral arteries caused a remarkable increase in the CAP threshold, which subsequently recovered following release of occlusion in all 10 animals. The threshold for acoustic stimulation at 60 minutes after recirculation was, however, higher than that in the preischemic state. Glutamate concentration in the perilymph was measured using a microdialysis technique followed by enzyme cycling analysis. Before occlusion, the glutamate level of the perilymph was 0.35±0.22 pmol/μl in the scala tympani (n=12) and 0.42±0.32 pmol/μl in the scala vestibuli (n=6). Ischemic insult caused an immediate rise in the glutamate level, which rose further even after recirculation, reaching a maximum of 11.72 pmol/μl in the scala tympani (n=12) and 8.49 pmol/μl in the scala vestibuli (n=6). In four animals, the cochlea was processed for transmission electron microscopic study at 30 minutes after ischemic load. The ischemia induced swelling of the afferent auditory nerve endings and vacuolation of the inner hair cells. These results suggest that the release of glutamate in the perilymph may aggravate ischemia-induced hearing dysfunction.