The purpose of these studies was to determine whether human peripheral blood polymorphonuclear cells (PMNC) can be directly activated by lymphokines or bacterial products to lyse tumorigenic cells under in vitro conditions. Preparations of PMNC with different levels of purity were isolated by countercurrent elutriation. PMNC were incubated with recombinant interferon gamma and muramyldipeptide, with lipopolysaccharide, or with the synthetic lipopeptide CGP 31362. Only PMNC preparations containing 3-5% mononuclear cells lysed allogeneic melanoma cells. Homogeneous populations of PMNC did not. The addition of 5% monocytes to homogeneous populations of PMNC triggered PMNC-mediated tumor lysis. Cell-to-cell contact was not required in this process since culture supernatant of blood monocytes incubated with lipopolysaccharide (but not with medium) could trigger tumor cell lysis by PMNC. PMNC lysed both allogeneic tumorigenic (melanoma) and allogeneic nontumorigenic (fibroblast) cells, whereas activated monocytes lysed only tumorigenic cells. In conclusion, PMNC are triggered to lyse target cells by blood monocytes activated by bacterial products or by lymphokines.