The permeability barrier of the skin which prevents transcutaneous water loss and penetration of harmful drugs from the environment is localized in the horny layer of the epidermis. Multiple lipid bilayers obstructing the intercellular space of the stratum corneum fulfill this function. In contrast to cellular membranes consisting predominantly of phospholipids, these lamellae contain mostly ceramides, cholesterol and free fatty acids. The lamellae are derived from the contents of lamellar granules (LGs) which are synthesized in the viable epidermal layers by the keratinocytes. LGs display stacks of small disks each of which represents a flattened vesicle or liposome. Prior to terminal differentiation, the disks are exocytosed into the intercellular space and fused to form uninterrupted sheetlike lamellae. The singular lipid composition of LG-disks and of stratum corneum-lamellae reflects the multistage process of barrier formation. It also renders these structures well suited to provide for a barrier function.