The mechanism of salicylate ototoxicity has been not elucidated yet. Although there are evidences that temporary hearing loss induced by disturbance of cochlear microcirculation due to the inhibition of prostaglandins synthesis by salicylate, prostaglandins synthesis inhibitors such as mefenamate or meclofenamate show different electrophysiological changes from salicylate. Thus, the effect of prostaglandins on salicylate ototoxicity should be questioned. Sympathetic nerve is important for the regulation of cochlear blood flow, which is reduced by salicylate. To test the idea that the change of autonomic nervous function of the inner ear has a major role in the mechanism of salicylate ototoxicity, the change of concentrations of catecholamine in the perilymph was evaluated. Sodium salicylate(460mg/kg) was injected intraperitoneally into albino guinea pigs. Five hours after injection, concentrations of catecholamine in the perilymph were measured in the left ear. Concentrations of salicylate in the perilymph of the right ear and the serum were measured to verify that the experimental animals had salicylate ototoxicity. For the control group, the same amount of normal saline was injected intraperitoneally, and concentrations of catecholamine in the perilymph were measured in both ears five hours after injection. Concentrations of catecholamine were measured by HPLC-EC and salicylic acid by fluorescence polarization immunoassay(FPIA). The concentration of an unknown compound which was not salicylic acid or its metabolites increased most prominently in the perilymph of the experimental animals. This compound increased by 70 times(p<0.01). This compound could be an unknown metabolite of catecholamine or a new neurotransmitter and might have a major role in the mechanism of salicylate ototoxicity. In the experimental group, norepinephrine was not detected because of the large peak of the unknown compound. However, the concentration of epinephrine in the experimental group was four times higher than that in control group(269±50.2ng/mL vs 67.2±22.6ng/mL). This was statistically significant(p<0.01). In conclusion, it is suggested that the increase of concentrations of the unknown compound might be important for the mechanism of salicylate ototoxicity. Also, the increase of concentration of epinephrine in the perilymph might have an additional role in the mechanism of salicylate ototoxicity.