The endolymphatic effects of perilymphatic ouabain (2 X 10(-3) M) were followed in 3 guinea pigs using ion-sensitive micro-electrodes, enabling a Na+-related permeability increase to be identified. Investigation of the strial ultrastructural changes in 11 more animals revealed early swelling of the marginal cells, while the intermediate and basal cells became shrunken with characteristically dark-staining cytoplasm. The subsequent cellular alterations were complex. The findings suggest that a major function of the Na+-K+-activated ATPase is preservation of the normal intracellular environment, inhibition resulting in widespread indirect effects. General measures of strial function, consequently, do not document just ATPase inhibition.