Human epidermis was separated from dermis by means of a suction blister device and dissociated with trypsin. The epidermal cell suspensions obtained contained 3--5% Langerhans cells as judged by immunofluorescence staining ot the cells with a rabbit anti-DR antiserum. The epidermal cells were co-cultured with purified allogeneic T cells and with autologous T cells with or without PPD of tuberculin. A strong T-cell response to allogeneic epidermal cells was obtained, as was a strong T-cell response to PPD, provided autologous epidermal cells were also present. Pre-treatment of the epidermal cells with anti-DR antiserum plus complement abolished both these responses. These data indicate that epidermal cells are able to substitute for macrophages both in the allo-activating and in the antigen-presenting function. Since the responsible cells were DR-positive, it is highly probable that the cells responsible for these functions are the Langerhans cells.