Monoclonal anti-T6 antibody, which reacts with the majority of cortical thymocytes but not peripheral T cells, also reacts with human epidermal Langerhans cells, as shown by a four-step immunoperoxidase method and immunoelectron microscopy. To define whether T6-positive cells are also present in normal human dermis, we used these techniques to demonstrate two immunologically distinct populations of histiocyte-like cells in normal human dermis. The first population contains cells devoid of phagolysosomes or Birbeck granules. These cells react with anti-T6 antibody, but not with monoclonal anti-T3 antibody which defines peripheral T cells, and are found predominantly in and around dermal lymphatic vessels. The second is composed of phagolysosome-containing cells which do not react with anti-T6 antibody or anti-T3 antibody. Because to date, Langerhans cells are the only cells in normal human epidermis that react with anti-T6 antibody, these data provide immunological evidence for a specific link between Langerhans cells and a T6-positive dermal mononuclear cell, possibly the so-called indeterminate cell. In addition, application of these techniques should, for the first time, permit the immunological distinction of these T6-positive mononuclear cells from other cells bearing Ia antigens, such as dermal histiocytes and certain lymphocytes, in normal and diseased skin.