Langerhans-cell-enriched epidermal cell preparations, when pulsed with antigen, can induce proliferative responses, in immune T cells, that are of the same magnitude as those induced by antigen-pulsed macrophages. Additionally, these cells bear surface receptors for Fc and C3b and display on their cell surface determinants encoded by genes of the I region of the major histocompatibility complex. Histological studies have implicated Langerhans cells in cell-mediated immune responses such as delayed contact hypersensitivity to 2,4-dinitro-1-fluorobenzene (DNFB). Langerhans cells play an important role in the induction of contact sensitivity. When murine epidermis that is naturally or artificially depleted of Langerhans cells is painted with DNFB, no sensitization occurs. More importantly, animals whose initial exposure to DNFB occurs through skin deficient in Langerhans cells are unable subsequently to mount effective hypersensitivity responses to this agent. We there believe that Langerhans cells function as peripheral antigen-presenting cells and that in their absence the host responds to antigen challenge by becoming specifically unresponsive.