To examine the reversibility of functional damage to the cochlea after transient ischemia, cochlear ischemia of 0-60 min was induced in 34 albino guinea pigs. Thresholds of auditory brainstem response (ABR) were then followed for 5 days after ischemia. Although the ABR threshold returned to almost the pre-ischemic value after 15 min ischemia, ischemia of 30 and 60 min duration induced irreversible dysfunction. Aminoguanidine, an inducible NO synthase (iNOS) inhibitor, significantly ameliorated the post-ischemic cochlear dysfunction induced by 60 min ischemia. Morphological findings of the hair cells were consistent with these functional results. These results indicate that ischemia of 30 min or longer induces irreversible damage to the cochlea and that iNOS plays injury-producing roles in this type of injury.