Langerhans cells constitute a morphologically well-characterized subpopulation (3--8%) of mammalian epidermal cells and, in contrast to the bulk of epidermal cells, bear Fc-IgG and C3 receptors, express immune response associated (Ia) antigens, and function as antigen presenting cells and allogeneic stimulatory cells to primed T lymphocytes. The purpose of this study was to define the ontogeny of Langerhans cells which has been a subject of considerable debate since their discovery in 1868. We have demonstrated that, after 3 weeks, most of the Langerhans cells in parental skin which had been transplanted onto F1 hybrids are of recipient origin whereas keratinocytes remain of donor origin, which indicates that the LC are derived from a mobile pool of cells. Furthermore, in studies of skin from radiation-induced bone marrow chimeric animals we have found that, depending upon the strain combination, up to 80% of the epidermal Langerhans cells are derived from the bone marrow of the donor animals. These studies indicate that epidermal Langerhans cells are derived from and are continuously replenished by a mobile pool of precursor cells which for the most part originate in bone marrow.