A broad basic study on skin was initiated to 1 determine the fundamental nature of the skin barrier, 2 elucidate the structure and mechanisms responsible for the selective resistance of skin to penetration by topical agents, and 3 select t pical agents or conditions leading to skin alterations that enhance or depress percutaneous absorption. Dramatic changes in the epidermis were noted in skin of rats deficient in linoleic acid. Keratinization process is impaired both the lucidum and corneum layers are infiltrated with fragments of nuclear material and even intact nuclei. The water diffusion rate is almost 10 times that of normal skin, and lactic acid penetrate such skin the latter cannot penetrate normal skin. The skin barrier presumed to be in the lacidum layer is defective in animals that are deficient in linoleic acid.