Langerhans cells (LC) constitute a small (2-6%) subpopulation of mammalian epidermal cells (EC) and are the only EC that bear Fc-IgG receptors and that share several other cell-surface characteristics and functional capabilities with cells of the monocyte-macrophage series. Since Fc-IgG receptor-positive macrophages are potent effector cells in antibody-dependent cellular cytotoxicity (ADCC), we determined whether LC-containing EC populations are also able to mediate ADCC. In the ADCC assay employed, BALB/c LC-containing EC at different effector/target cell ratios consistently failed to lyse bovine red blood cell (BRBC) targets which were either trinitrophenyl(TNP)-modified or not modified and reacted with an appropriate antibody: a purified rabbit IgG anti-BRBC, or a mouse or rabbit anti-TNP antiserum. In addition, LC-containing EC did not mediate mitogen-induced cellular cytotoxicity using purified phytohemagglutinin. BALB/c spleen cells, used as a positive control, gave substantial specific release in all experiments performed.