The effect of lipopolysaccharides (LPS), lipid A and interferon on cell-mediated cytotoxicity was investigated using 51Cr-labeled K-562 tumor cells as targets. As effectors, peripheral blood mononuclear cells from healthy blood donors were obtained by Ficoll gradient centrifugation: mononuclear phagocytes were eliminated by iron phagocytosis and plastic adherence. A T cell-enriched population was obtained by passing mononuclear phagocyte-depleted mononuclear cells through nylon wool columns. LPS and lipid A augmented cell-mediated cytotoxicity provided mononuclear phagocytes were present. Supernatants from LPS-treated mononuclear phagocytes and T cells enhanced mononuclear phagocyte-mediated cytotoxicity to a higher degree than LPS and lipid A alone. This finding suggests the participation of a lymphokine. In contrast, the interferon preparation increased the cell-mediated cytotoxicity both of mononuclear phagocyte-containing and of mononuclear phagocyte-depleted effectors. Here, the participation of natural killer cells as effectors is suggested.