Numerous electron microscopic studies have demonstrated that the plasma membranes of keratinizing epithelial cells undergo striking morphological changes. From a more or less symmetrical, trilaminar structure similar to that described for most cells, the membrane undergoes a marked increase in thickness and becomes highly resistant and impervious to the action of strong reagents. In the present electron microscopic study on rat tongue epithelium, this membrane thickening was observed to begin by the appearance within cells of a moderately dense band of material, about 100 A thick, in the peripheral cytoplasm against the intracytoplasmic face of the plasma membrane. This peripheral dense band was observed in epithelial cells each of which stiU possessed a nucleus and all its usual cytoplasmic organelles. Following its initial appearance, this peripheral intracytoplasmic band increased in density so that it became indistinguishable from the inner layer of the plasma membrane. The electron microscopic image at this stage gave the impression that the inner layer of the plasma membrane had undergone a considerable increase in thickness, whereas the outer and middle layers had remained essentially unchanged. Finally, in fully keratinized cells, the outer layer of the plasma membrane was not always demonstrable, so that in these cells the plasma membrane seemed to be corn. posed of a single thick, dense layer of membrane material. The possible implications of these membrane alterations in the total process of keratinization are discussed.