The cutaneous manifestations of essential fatty acid (EFA) deficiency in the rat include scaling of the paws and tail and enhanced permeability of the skin. Since there is an apparent defect in the epidermal barrier, a histochemical survey of the metabolic and enzymatic changes which accompany the gross picture of EFA deficiency was undertaken. Consistent differences between control and EFA-deficient animals were observed with Sudan black, Baker's acid hematin, acid phosphatase, Giemsa, and toluidine blue staining. These histochemical differences appear in and above the granular layer in the area believed to contain the epidermal barrier. The results of the present study suggest a derangement of phospholipid metabolism in the skin of EFA-deficient rats. The skin of the EFA-deficient animal appears to be an excellent experimental model for study of the epidermal barrier.