In an attempt to modulate the recognition processes that occur on lymphocyte membranes in mixed lymphocyte culture, responding cortisone resistant thymocytes or stimulating spleen cells (treated with mitomycin C) were pretreated with native concanavalin A (N-Con A) or succinyl-Con A (S-Con A). Highly significant cell proliferation was observed in syngeneic combinations when either the responding cells or the stimulating cells were so treated with Con A, although Con A pretreatment alone was never mitogenic. In allogeneic combinations the proliferative response with Con A pretreatment of either partner on day 3 was five to seven times higher than in the normal mixed lymphocyte reactions. The triggering of proliferation was dependent on two factors: (a) The presence of spleen cells as the stimulating cells (thymocytes were much less effective). (b) The binding of Con A molecules to either one of the partners, the effect being abrogated by the specific inhibitor of Con A, alpha-mannopyranoside. The optimal concentration of S-Con A was about twice that of N-Con A. Even more striking was the observation that cultures in which either one of the partners was pretreated with Con A in allogeneic combinations showed a strong suppression (60-80% inhibition) in the subsequent generation of the cytotoxic lymphocytes (CL). The Con A concentration required to trigger a proliferative response corresponded to that for suppressing the generation of CL. Con A pretreatment did not result in a cytotoxic activity toward syngeneic tumor cells.