To gain insight into the mechanism of noise induced permanent threshold shift (PTS), the magnitude of the auditory threshold elevation induced by injection of salicylic acid (which competitively binds with the motor protein prestin) to animals with a pre-existing PTS was compared to that in control animals (not exposed to noise). Normal mice were exposed to a noise intensity and duration which causes a small PTS. After determining the degree of the resulting PTS two weeks following the noise, salicylic acid was injected. The salicylic acid induced an additional threshold elevation and its magnitude was compared to that in control mice which had not been noise exposed. The mean noise induced PTS in the experimental (noise exposed) group was 25.5 dB. Following the administration of salicylic acid to these animals, there was an additional (salicylic acid induced) mean threshold elevation of 17.5 dB, and this was significantly smaller than that in control (not noise exposed) mice (36.8 dB). This may be evidence for a reduced number of salicylic acid binding sites on prestin and therefore the PTS may be due to disruption of prestin by the free radicals produced during the noise exposure.