A tissue is said to be differentiated when it has begun to synthesize characteristic macromolecules for that tissue. In some tissues, specific proteins have been well characterized, and their appearance during histodifferentiation can be monitored and assayed in minute quantities. In keratinizing epithelium the appearance of constitutive proteins during differentiation has been monitored in epidermis but not in oral epithelium. We have identified and purified a soluble, low molecular weight, acidic protein in bovine lingual epithelium. This protein has an apparent molecular weight of 8,200 plus or minus 400 daltons, and isoelectric point at pH 4.7, and an amino acid composition very similar to that of fibrous alpha-keratins. An antibody to this protein has been made. In immunohistochemical studies, stratified squamous epithelia from several mammalian sources exhibit reactivity with the antibody. In the proposed experiments, the major goal is to determine the relationship between the low molecular weight, soluble protein and the insoluble fibrous alpha-keratins. These data will contribute to the understanding of the correlation between structure and biochemistry of oral epithelium and similar epithelia in other parts of the body. Moreover, they could form the basis for a biochemical classification of normal and pathological tissues.