The skin is not only a physico-mechanical barrier between the environment and the body, but it also functions as an immune organ. The immunological function of epidermis is principally linked to the presence in this tissue of a distinct subpopulation of dendritic cells: the Langerhans cells (LC). LC constitute 2-4% of epidermal cell population and within epidermis they are the only cells which express MHC class II antigens constitutively. LC play a key role in the initiation of T cell responses to cutaneous antigens by picking up the antigen and migrating to the draining lymph node where they trigger specific T cell activation. There is also evidence that keratinocytes participate in immune responses in the skin since these cells produce a wide variety of cytokines that can modulate T cell responses. Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin and mucosa (Langerhans cells), and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the out-growth of dendritic cells from mouse peripheral blood. The cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder. Recent studies reported that after 2-3 days in vitro incubation, both murine and human LC undergo profound phenotypic changes, as an enhancement in the expression of MHC class I and II antigens, LFA-3 and ICAM-1 molecules, a concomitant decrease of CD1a antigens and a loss of Fc gamma RII. Furthermore, cultured LC (cLC) lose or markedly reduce their specific cytoplasmic organelles: the Birbeck granules. Therefore, after a 2-3 days in vitro incubation, LC seem to acquire most of the features of lymphoid dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS)