Endocochlear DC potential (EP) and cochlear microphonics (CM) in the guinea pig under the influence of the divalent heavy metal cations of manganese, nickel, cobalt and cadmium, and the trivalent cation of lanthanum were investigated. The area from the scala tympani to the scala vestibuli was perfused with control and test solutions. CM decreased gradually to 50-80%, but EP showed no change after perfusion with a solution containing 1 mM of metal ions. At a concentration of 10 mM, EP decreased from 80 mV to 10-20 mV and CM decreased to 15-55%. At 100 mM, EP increased by about 10 mV at the beginning of perfusion, remained steady for 1 min, and then rapidly decreased to 0-10 mV. Meanwhile, CM continued to decrease, finally sustaining a 10-56% reduction. The decrease in EP and CM were irreversible, and perfusion of the area with the standard solution for 20 min had no effect. The osmolarity of the artificial perilymph containing 100 mM of metal ions was twice as high as that of the normal physiological solution. The effects of osmolarity, however, were excluded because perfusion with an artificial perilymphatic solution made hypertonic by either NaCl or sucrose changed neither EP nor CM. The application of 100 mM of metal ions topically to the round window membrane caused no change in EP. The alkali metal ions are known to inhibit inward Ca2+ current. Therefore, the present results suggest that Ca2+ ions play a role in maintaining EP generation in the stria vascularis and CM generation in the organ of Corti.