Langerhans cells constitute a minor cell population within the mammalian epidermis. This paper defines these cells immunologically and functionally and supports the concept that Langerhans cells are closely related to cells from the monocyte-macrophage-histiocyte series. Both cell types bear surface receptors for Fc-IgG and C3 and express surface glycoproteins, termed Ia antigens, encoded for by immune-response genes (Ir genes) of the major histocompatibility complex of the species. The expression of Ia antigens by Langerhans cells and macrophages is intimately associated with important functions of both cell types, including the capacity to present immunologically relevant antigen to the T lymphocyte and to cause proliferation to allogeneic T lymphocytes in mixed leukocyte reactions.