Concanavalin A (Con A) activates nonimmune human lymphocytes in vitro to undergo transformation, DNA synthesis, and lymphotoxin (LT) secretion. LT secretion is inhibited (within minutes) when free and membrane-bound Con A are removed by washing or incubation with the competitive inhibitor, α-methyl mannoside. LT secretion can be reinitiated by addition of fresh Con A. While LT can be rapidly regulated, blast transformation and cellular DNA synthesis are under less restrictive control. Although they appear to be related, LT secretion and lymphocyte transformation seem to be regulated by independent control mechanisms. These studies indicate that recognition and contact of lymphocyte membrane sites initiate as well as regulate the efferent or destructive phase of cell-mediated immune (CMI) reactions. A model of how lymphocytes could employ LT in specific and nonspecific cytodestructive CMI reactions is presented. © 1974.