Studies on the polypeptide chain compositions of human stratum corneum and callus have shown that characteristic modifications of the epidermal fibrous protein occur during normal eqidermal keratinization. The polypeptide chain composition of psoriatic scale differs from that of both normal stratum corneum and callus. A major constituent, the alpha-chain (Mr = 70 000) of the epidermal fibrous protein is either absent or greatly decreased in amount in psoriatic sacle. This chain is, however, present in normal amounts in the uninvolved epidermis of psoriatics and, during effective treatment, returns to normal levels in the previously involved areas. It is concluded that this is a major, reversible difference between involved psoriatic epidermis and uninvolved psoriatic or normal epidermis and that it most probably results from a defect in the synthesis of the alpha-chain.