The action of the substance P agonist, substance P methyl ester (SPME) on cochlear potentials was examined in the guinea pig. Previous studies have shown that SPME is a selective agonist for neurokinin 1 (NK1) receptor. Perfusion with SPME at a concentration of more than 10(-6)M produced an increase in the amplitudes of the compound action potential and negative summating potential in a dose-dependent manner. N1 latency showed a tendency to be shortened, but this change was not significant. Amplitudes of the cochlear microphonics and endocochlear potential remained unchanged. Substance P fragment 7-11, an inactive analogue, produced no changes in the cochlear potentials. In contrast, the substance P antagonist [D-Pro2, D-Trp7,9]-SP blocked the action of SPME on the cochlear potentials. These results suggest that substance P may modulate neurotransmission through NK1 receptors in the cochlea.