Epidermal Langerhans cells (LC) are Birbeck granule-containing bone-marrow-derived cells, which are located mainly in the suprabasal layer of the epidermis. They can be readily identified by their strong expression of CD1a and MHC class II molecules. In addition to these 'classical' properties, an extensive phenotypic profile of normal human LC, summarized in this review, is now available. The powerful capacity of LC to activate T lymphocytes is clearly documented and, to date, LC are recognized as the prominent antigen-presenting cells of the skin immune system. They are generally believed to pick up antigens encountered in the epidermis and to migrate subsequently from the epidermis to the skin-draining lymph nodes. Upon arrival in the paracortex of lymph nodes, the antigen-laden LC transform into interdigitating cells and they present antigen to naive T lymphocytes in a MHC class II-restricted fashion; this results in the generation of antigen-specific immune responses. It has also been demonstrated that transformation of LC into interdigitating cells occurs when LC are cultured in vitro. Both in vivo and in vitro studies have indicated that properties of LC, such as phenotype, morphology and the stimulatory potential to activate T lymphocytes, are dependent on the local microenvironment in which the LC reside. The essential role of LC in the induction of contact allergic skin reactions and skin transplant rejection is well established.