Lanthanides are rare earths, elements 55–71 in the periodic table, that are of interest in biologic systems as isomorphic competitors for calcium binding sites. Lanthanides were tested for their inhibitory influence on the Ca++/Mg++-dependent ATPase of epidermal langerhans cells in vitro, and on the immunologic function of Langerhans cells in vivo. The trivalent ions of lanthanides, lanthanum and cerium completely inhibited the ATPase staining of Langerhans cells in vitro. When mice were sensitized with dinitrofluorobenzene on skin sites pretreated with topical lanthanum chloride, and challenged on untreated ear skin, a markedly reduced contact hypersensitivity response was observed. This hyporesponsiveness was found to be antigen specifics and could be passively transferred to naive syngeneic animals recipients by CD4- CD8+ spleen cells. These results suggest that inhibition of the epidermal Langerhans cell surface ATPase by application of topical lanthanum and the induction of antigen-specific immunologic tolerance may be related events.