Immunohistochemical identification of intracellular keratin was achieved using an indirect antibody technique on paraffin-embedded human tissue. A study of numerous tissues confirms that keratins are abundant in all layers of squamous epithelia, in the ducts of epithelial-derived glands, and in the epithelia of the respiratory and urinary tracts. Using an immunoperoxidase technique which offers increased histologic resolution, we have shown that the basal or reserve cells of the tracheal, bronchial, prostatic, and cervical gland epithelia are the predominant keratin-containing cells in these tissues. The normal differentiation of basal cells into nondividing, superficial columnar cells is accompanied by the loss of cytoplasmic keratin proteins. Foci of epithelial squamous metaplasia stain intensely with antikeratin antibodies and presumably represent an exaggerated proliferation of the keratin-containing basal cells. Alveolar respiratory epithelium, acinar cells of various glands, and many mesodermal tissues (muscle, hematopoietic, and lymphoid tissue, nerve, and connective tissue) were devoid of keratin proteins. The ability to identify keratin proteins within fixed, embedded tissue (including those known to lack tonofilament bundles) may prove useful in the study of tissue histogenesis and carcinogenesis, and in the pathologic assessment of poorly differentiated malignant neoplasms and tumors of controversial cellular origin.