The acute and chronic effects of treatment with ethacrynic acid (EA) and furosemide (FU) on the structure of the murine endolymphatic sac were studied by means of light and transmission electron microscopy. The animals were treated with loop diuretics in doses which are known to cause morphological alterations of the stria vascularis and a significant reduction of the endocochlear potential. A single intravenous injection of either EA or FU resulted in immediate morhpological changes such as an increase in cytoplasmic contents of endoplasmic reticulum and more prominent Golgi structures of the light cells. These cells developed membrane-bound granules and a smooth tubular network in the apical cytoplasm. These findings together with the appearance of a precipitate on the luminal aspect of the cell membrane suggested secretory activity. Ten days after daily intraperitoneal injections with loop diuretics in sub toxic doses, the epithelial cytoarchitecture of the endolymphatic sac was altered, with pronounced veiling of the light cells by the dark cells. It is concluded that the changes in the endolymphatic sac epithelium after treatment with ototoxic diuretics may not be a result of a primary toxic effect on the sac per se, but rather be secondary to alterations in fluid and ion homeostasis in the rest of the inner ear.