Intercellular and skin-surface substances, and exfoliating corneocytes, were clearly visualized by both light and electron microscopy. The intercellular space constituted an essential part of the normal human stratum corneum, in the basal and middle zones of which this space was filled with substances producing a compact appearance. The intercellular constituents were a nonhomogeneous substance, intact, single and "compound" lamellar granules and an intensely stained, membrane-like material that in some parts, but not in others, had a lamellar pattern. The artifacts produced by ultrathin sectioning for electron microscopy were too small to provide sufficient explanation for the porous appearance of the superficial zone. More important factors seemed to be enlargement of the intercellular space with decrease in the number of desmosomes and alterations of the intercellular substances, with decrease in the amount of nonhomogeneous substance and transformation of the single and "compound" lamellar granules into single and "compound" vesicular bodies. The hypothesis is advanced that the single and "compound" vesicular bodies together with the decreased amount of nonhomogeneous substance may contribute to maintain the patency of the intercellular space in the superficial zone (stratum disjunctum), thereby facilitating absorption of surface-applied agents into the stratum corneum by some shunt mechanism, while the content of the intercellular space in the basal and middle zones (stratum compactum) forms the principal barrier to free diffusion.