The antigenic properties of epidermal Langerhans cells (LC) were determined and compared with those of non-lymphoid dendritic dermal cells (DDC), interdigitating reticulum cells (IRC), dendritic reticulum cells (DRC), and histiocytic reticulum cells (HRC) by examination of serial and double immunoenzymatic and -fluorescence stained frozen sections of skin and lymph node biopsies. All of these cell types expressed leucocyte common antigen. LC, DDC, and IRC demonstrated similar antigenic phenotypes (HLA-DR+, Leu3+, OKT6+/-, anti-C3 receptor-, R4/23-, Ig-complex-, MO2-), whereas the antigenic properties on DRC (HLA-DR-, Leu3-, OKT6-, anti-C3 receptor+, R4/23+, Ig-complex+, MO2-) and HRC (HLA-DR+/-, Leu3-, OKT6-, anti-C3 receptor+ R4/23-, Ig-complex+, MO2+) were markedly different. These data suggest that LC, DDC, and IRC are closely interrelated cell types, and support the concept that DRC and HRC are unique cell types which do not appear to be related to LC, DDC, or IRC. The lack of labelling of LC with monoclonal anti-C3b receptor antibody, and polyclonal antiserum recognizing C3b, C3bi, and C3d receptors strongly indicate that the EAC-rosetting of LC previously described is not due to the presence of C3 receptors on these cells. Alternatively, LC may express C3 receptor molecules different from those previously identified (C3b, C3bi, and C3d).