Monocytes have a nonoxidative mechanism of tumor cytolysis operative in CGD and in normal monocytes under anaerobic conditions. The absence of competitive inhibition provides negative evidence for a contact-independent mechanism of cytolysis, confirmed by the demonstration of a soluble mediator secreted independently of effector-target cell contact. This cytolytic monokine, a protein of apparent molecular weight between 25,000 and 40,000, resembles TNF functionally and antigenically. Further work will be required to demonstrate its biochemical identity, its precise mechanism of toxicity, and the extent of its importance in vivo.