Polymorphonuclear leukocytes (PMN) are able to exert cell-mediated cytotoxic reactions in order to eliminate tumor cells and virus-infected cells. Appropriate stimulation is needed to activate the potential cytotoxic arsenal of the PMN in contrast to the spontaneous cytotoxicity mediated by natural killer cells. Stimulation with phorbol esters induces an oxygen-dependent killing mechanism which results in highly efficient lysis of red blood cell targets. Tumor target cells are more resistant to oxygen-dependent killing mechanisms due to effective antioxidant capacities. Antibody-coated tumor target cells are easily recognized and bound by PMN via a cooperative action of Fc receptors and adhesion molecules. This firm contact and receptor occupation result in efficient killing of the tumor cells which does not require production of oxygen radicals. The mechanisms of PMN-mediated cytotoxicity are discussed and compared with data known from natural killer cells and monocytes.