We intend to continue our multidisciplinary approach to the study of the permeability barrier in mammalian epidermis, utilizing standard ultrastructural techniques, freezefracture replication, lipid cytochemistry, and tracer perfusion of normal, experimentally perturbed, and pathological skin. Our earlier work in the neonatal mouse will be extended to human skin, using identical methodology. Moreover, in collaboration with Dr. N. Nicolaides, we will isolate and characterize lipids from mouse and human epidermal barrier layers. Since the intercellular lipids of the outer epidermis appear to be derived from secreted lamellar body contents, these structures will be isolated and their contents characterized. Then the capability of various families of previously isolated barrier layer lipids to retard water loss will be assessed both in vitro and in vivo by measurement of transepidermal water loss following application of isolated lipids to experimentally perturbed and diseased skin. Furthermore, the pathways of percutaneous transport of both lipid- and water-soluble materials will be analyzed morphologically utilizing fluorescence microscopy, soluble-tracer autoradiography, in situ precipitation, and in vitro perfusion techniques. Finally, in order to pinpoint factors which control both the cohesion as well as the ultimate, orderly desquamation of normal stratum corneum, we will analyze the lipid phase-transition properties of isolated barrier layer lipids and outer epidermal sheets by differential thermal analysis and electron spin resonance. This work may lead to the development of: 1) the ideal burn wound-barrier dressing; 2) an optimal delivery system for topical medications; and 3) correction of many scaling skin diseases.