The effect of endoplasmic Ca2+-ATPase inhibitors on cochlear potentials was examined in the guinea-pig. Perilymphatic perfusion with thapsigargin (10[-6] M) produced a significant decrease in the amplitudes of cochlear microphonics, negative summating potential and compound action potential, and a significant prolongation of N1 latency with no change in the endocochlear potential. These changes were all dose dependent. Another endoplasmic Ca2+-ATPase inhibitor, cyclopiazonic acid (10[-5] M), produced the same effects as thapsigargin on cochlear potentials. These results suggest that endoplasmic Ca2+-ATPase inhibitors may have inhibitory functions on cochlear potentials.