To investigate whether elimination of the medial efferent system influences permanent threshold shift following noise exposure, we developed an animal model in which strychnine was chronically delivered into the cochlea via an osmotic pump. Pigmented female guinea pigs were allocated into three groups: group I was treated with strychnine (50 microM, 0.5 microl/h, 14 days) in the left ear and exposed to noise (105 dB SPL broadband, 3 h) 3 weeks after the cessation of the strychnine perfusion; group II received strychnine in the left ear but no noise exposure; group III was treated with Ringer's solution in the left ear and exposed to noise. Animals in group II developed no hearing loss after the strychnine perfusion. The operated ears in group I demonstrated greatest hearing threshold shift 3 h after noise exposure. Hearing recovered during 2 weeks after noise exposure in both operated and non-operated ears in groups I and III. Two weeks after noise exposure, the operated ears in group I showed significantly greater threshold shift at 12, 16, and 20 kHz compared to the operated ears in group III and non-operated ears in groups I and III. These findings suggest that chronic strychnine administration into the cochlea inactivates the medial efferents without changing hearing threshold and that the medial efferents help to protect against permanent threshold shift following noise exposure.