Mutual in vitro cell destruction resulted when nonimmune or immune mouse or rat small lymphocytes were attached to genetically dissimilar target cells with phytohemagglutinin or xenogeneic antibody. The ability to induce this reaction resided only with viable cells of lymphoid origin. The step(s) leading to aggressor-target cell destruction observed in these studies is suggested by the following sequence: a) attachment of the aggressor cell to the target cell, b) membrane site(s) interaction between the lymphocyte and target cell which serves as a recognition step and if the target cell is not recognized as “self,” d) a “triggering” of aggressor lymphocyte activity which results in enlargement of the lymphocyte and release of a soluble toxic factor termed “lymphocyte cytotoxic factor” (LCF). LCF may be the agent responsible for the death of both cells.