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Background & Objectives:Nitric oxide has been sugested to play an important role in the pathogenesis of cisplatin ototo-(NG-Nitroarginine Methyl Ester) is an inhibitor of nitric oxide synthase. MK-801 (Dizocilpine Maleate) is a NMDA receptor antagonist. To evaluate a role of nitric oxide in cisplatin ototoxicity, we investigated whether L-NAME and MK-801 can block the cisplatin ototoxicity in guinea pigs. Materials & Method:In the Group 1, normal saline was in-jected intraperitonealy as a control group. Group 2, 3, 4, and 5 were injected intraperitonealy as described in the folowing:Group 2, cisplatin only; + cisplatin;Group 4, MK-801+ cisplatin;Group 5, L-NAME+ MK-801+ cis-platin. Using an auditory brainstem response, hearing threshold was tested before cisplatin administration and 5 days after cisplatin injection in each group. The morphological changes of the cochlea were observed by scanning electron microscopy. Results:In the Group 2, a significant hearing loss was observed comparing to Group 1. In contrast, Group 3, 4, and 5 did distorsion and loss of stereocilia of the hair cells. However, the Group 1, 3, 4, and 5 demonstrated well preserved cochlear hair cell morphology. Conclusion:Hearing loss induced by ototoxicity of cisplatin was prevented by L-NAME and MK-801. This study suggests that NO may mediate cisplatin ototoxicity. (Korean J Otolaryngol 2002;45:741-6)