We are studying both the mechanisms which permit activation of sensitized lymphocytes to become cytotoxic effector cells and the cytotoxic process itself. One physiologic control mechanism regulating immune expression is immunologic enhancement. An estimate of in vivo enhancing ability can be obtained from in vitro blockade of the mixed leucocyte culture reaction. However, we have demonstrated that serum which is very specific in its in vivo enhancing effect (L anti-BN serum enhances LBN F1 kidneys placed in Lewis animals, but not LxBuffalo F1 hybrid kidneys) causes blockade of both specific and nonspecific reactivities in vitro. Thus, not only is LxLBN blocked, but also LxLBu, as well as activation by PHA and antigen. There is now abundant evidence that lymphotoxin mediates lymphocyte-mediated cytotoxicity. This is demonstrated by a new assay for LT which measures the death of 250-500 cells. In vitro cytotoxic systems in which 25-75 percent of the cells are killed contain proportionate amounts of soluble lymphotoxin, regardless of the method used to activate the lymphocytes (PHA, specific antigen, in vivo sensitization). Furthermore, rabbit anti-LT completely abrogates these cellular cytotoxic systems.