Tissue macrophages are bone marrow derived mononuclear cells which play an important role in the immune response, especially as antigen presenting cells. They comprise a heterogeneous population of cells with phagocytic activity. On morphological functional and cytochemical criteria it is likely that the Langerhans cell (LC) in the epidermis, the veiled cell (VC) in the afferent lymph and the interdigitating cell (IDC) in the thymus dependent area of peripheral lymphoid organs and the thymus medulla belong to a subpopulation of the macrophages. They are low phagocytic, Ia positive and are highly immunogenic. VC and IDC may contain Birbeck granules, the characteristic organelles of the LC, suggesting a relationship between these cell types. An epithelial micro-environment as present in the skin epidermis and the thymus is necessary for the induction of these granules, which appear to have no immunological significance. In a scheme the development from monocyte into LC or into VC and subsequently IDC is postulated. Probably VC transport antigen from the skin area via the afferent lymphatics into the draining lymph node. In the thymus dependent area of this organ they present this antigen to T cells and mature into IDC. IDC in the medullary area of the thymus may also be involved in antigen presentation to immunocompetent T cells. However, in this central lymphoid organ a function in instruction of helper T cells may not be excluded.