Functional studies on native human dendritic cells (DCs) are hampered by technical difficulties in preparing fresh DCs. Recently, with the help of the monoclonal antibody M-DC8, we succeeded in isolating a major subpopulation of human blood DCs by a one-step immunomagnetic separation procedure. These cells strongly express FcγRIII (CD16) and FcγRII (CD32) and are quite efficient in the antigen specific activation of naive T cells. Because some Fcγ receptor-bearing cell types are known as effector cells in antibody-dependent cellular cytotoxicity (ADCC), we investigated whether M-DC8⁺ DCs are capable of effectuating ADCC. In this report we show that freshly prepared M-DC8⁺ DCs efficiently mediate tumor directed ADCC and that both types of Fcγ receptors as well as tumor necrosis factor α essentially contribute to the cytotoxic activity. The results provide evidence that, in addition to their pivotal role in primary T-cell activation, a subset of blood DCs displays efficient cytotoxicity in ADCC.