Recent investigations have shown that anti-IL-2 receptor antibodies can prolong cardiac allograft survival in animal models and can be used effectively as primary immunosuppressive therapy in human renal transplantation. While previous studies have established that helper and cytotoxic T cells require IL-2 for proliferation, the role of this lymphokine in suppressor cell development is uncertain. We therefore studied the effects of SA36.6G (a monoclonal antibody directed at the 55 kD chain of the high-affinity IL-2 receptor) on events occurring in the mixed lymphocyte reaction. As expected, when added at culture initiation, SA36.6G inhibited both the proliferative response to allogeneic stimulation, and the generation of cytotoxic T cells. These effects were not the result of altered growth kinetics. In contrast, the generation of suppressor cells with a polymorphic pattern of specificity was not blocked by SA36.6G. Cultures containing SA36.6G had decreased numbers of activated lymphoblasts, but among this activated cell population the proportion of 2H4+ cells was doubled (53 +/- 13% vs. 27 +/- 9%). SA36.6G also blocked the appearance of IL-2 receptors on activated cells as determined by flow cytometry. This relative sparing of suppressor cells by an anti-IL-2 receptor antibody suggests that these cells may either exhibit IL-2 independent proliferation, or utilize an IL-2 receptor not recognized by SA36.6G.