Dendritic cells (DC) are potent antigen-presenting cells that are important for the priming of antitumor cytotoxic T cells. Recent reports suggest that DC may also have direct cytotoxic effector functions against selected tumor-cell lines by mechanisms that are dependent on dendritic cell–tumor cell contact in vitro. The authors report that ex vivo-generated murine DC induce the apoptosis of a panel of syngeneic and allogeneic murine tumors. Apoptosis of the MCA205 fibrosarcoma tumor-cell line by C57BL/6-derived DC was not mediated by Fas/FasL interactions and, in contrast to other studies, DC–tumor cell contact was not required to effect tumor-cell killing by DC. Therefore, the authors postulated that tumor-cell killing was mediated by an apoptotic factor that was secreted by DC. Even though DC did not secrete such apoptotic cytokines as interferon-&agr; or tumor necrosis factor-&agr;, they did secrete nitric oxide, and tumor apoptosis was partially abrogated by the nitric oxide synthase antagonist NG-monomethyl-L-arginine. Therefore, the authors' data demonstrate a novel mechanism for DC-induced tumor-cell apoptosis that does not require DC–tumor cell contact and is partially mediated by nitric oxide.