We have observed that monoclonal antibodies directed against human Ia-like antigens react with a subset of epidermal keratinocytes as well as Langerhans cells in normal human skin. Membrane reactivity for HLA-DR antigen in flattened ductal keratinocytes and in adjacent cuticular cells forming the acrosyringial lumen was observed using immunoelectron microscopy. It should be recognized that Ia-positive acrosyringial keratinocytes represent a potential source of contamination in methods designed to study and isolate Langerhans cells using antibodies directed against HLA-DR antigens. Teleologic considerations of HLA-DR antigen expression in the acrosyringium are discussed