In all mammalian species so far examined, Langerhans cells or their precursors are the only epidermal cells expressing Ia antigens or their equivalents. In man, xenoantisera raised in rabbits against purified B lymphocyte cell membrane antigens were utilized to stain the Langerhans cells, by either fluorescence or immunoferritin methods. A high proportion of the indeterminate cells in the epidermis also expressed HLA-DR antigens, and a relationship to Langerhans cells is suggested. Confirmation of these results was obtained in mouse. Alloantisera raised against I-A and I-EC subregion products again stained only Langerhans cells. Fluorescence, immunoperoxidase, and immunoferritin methods were used, and confirmation of the specificity of the reaction was achieved at the electron microscope level. Langerhans cells were shown, by ATPase staining, to be absent from the epithelium of the central cornea, but were present in the limbus. Population of the entire corneal epithelium surface was induced by application or irritants or contact sensitizing agents such as dinitrochlorobenzene. Grafting of corneas either deficient or populated with Langerhans cells, to skin beds, may answer the question of the influence of such cells on allograft rejection.