Loricrin, the major component of the cornified envelope, is normally expressed in the granular layer of epidermis during the last steps of keratinocyte differentiation. Using an antiloricrin antiserum (A8-73), an increased expression of this envelope precursor was found in some disorders of hyperorthokeratosis (ichthyosiform erythroderma; lichen ruber), but not in others (keratodermia ichthyosis vulgaris). In disorders accompanied by parakeratosis, a sign of incomplete differentiation (psoriasis, prurigo nodularis) loricrin was not detected, whereas the tissue expressed filaggrin. Treatment of normal skin with retinoic acid, increasing epidermal thickness in some subjects, led to an increased expression of loricrin. Loricrin might be a useful indicator of the extent of terminal epidermal differentiation in skin disorders.