The immunoperoxidase method for involucrin detection was applied to the study of the maturation of epithelial lesions of the oral mucosa that included specimens of leukoplakia, lichen planus, verrucous carcinoma, carcinoma in situ and invasive carcinoma. Areas of orthokeratinized, parakeratinized, and non-keratinized normal mucosa were also studied. Normal orthokeratinized epithelia showed intracytoplasmic or pericellular staining in the suprabasal epithelial layers in a pattern similar to that of the normal epidermis. Parakeratinized and non-keratinized epithelia were less stained. Intense staining was observed in leukoplakia, whereas the staining of lichen planus was less intense but exhibited a more homogeneous pericellular staining pattern than leukoplakia. Verrucous carcinoma was markedly and very irregularly stained. Carcinomas in situ and invasive carcinoma exhibited a slightly positive and patchy reaction. The distribution patterns of involucrin in the lesions correlated very well with the degree of epithelial differentiation. In addition, irregular patchy distribution correlated with the degree of atypia, and was especially evident in carcinomas.