Langerhans cells and indeterminate cells are the unique antigen-presenting epidermal cells participating in human lympho-epidermal interactions. They bear class II HLA-DR molecules, can substitute for macrophages in antigen presentation, induce a T-cell proliferative response to antigens and haptens in sensitized donors, and are necessary for alloantigen T-cell activation and generation of alloreactive cytotoxic T cells in vitro. Indirect immunofluorescence and immunogold electron microscopy on class II positive epidermal cell enriched suspensions (panning, FACS) indicated two populations of DR-positive epidermal cells: strongly DR-positive cells (25-30, 8% of positive epidermal cells) and faintly DR-positive cells, with a density of surface DR sites of respectively 5 X 10(5) and 1 X 10(5). Most Langerhans cells are among this second group while indeterminate cells are usually strongly DR-positive. OKT6-labelled cells were only typical Langerhans cells.