The involvement of crossed cochlear pathways in modulating the deafening effects of loud sound was investigated in the anaesthetized guinea pig. Auditory nerve activity was blocked unilaterally, either by surgical cochlear destruction or intracochlear perfusion of lignocaine, and the effect of a standard loud sound exposure in the untreated ear was then assessed using the compound action potential (CAP) audiogram technique. It was found that both cochlear destruction or lignocaine perfusion reduced the amount of threshold elevation in the untreated ear. The effect of lignocaine perfusion was significantly greater than acute cochlear destruction. In animals allowed to survive for 24 h and one week post-cochlear destruction before loud sound exposure, the protective effect was still present and was significantly greater than immediately post-destruction. This long-term protective effect of contralateral cochlear destruction was blocked by administering strychnine prior to the loud sound exposure. The results of lignocaine perfusion and chronic destruction make it unlikely that protection immediately post-destruction is the result of a transient barrage of primary afferent activity. We conclude that elimination of auditory nerve input can alter the effectiveness of brainstem circuitry responsible for protection (possibly the olivocochlear system). Since acoustic stimulation of the contralateral ear also has acute protective effects thought to be mediated by olivocochlear efferents, the circuitry responsible for protection appears to be subject to a complex balance between excitatory and inhibitory influences.