Recombinant interleukin 4 (rIL4) inhibited the proliferation and induction of lymphokine activated killer (LAK) cells in human peripheral blood mononuclear cells (PBMC) cultured in recombinant interleukin 2 (rIL2). Other recombinant cytokines, such as rIFN gamma, rTNF alpha, rIL1, and rIL3, did not inhibit LAK cell induction. rIL4-mediated suppression was dose dependent. As little as 1 U/ml of rIL4 significantly decreased both LAK activity and proliferation of cells induced by incubation of PBMC with 200 U/ml rIL2. Suppression was specific for the induction phase of LAK activity, because rIL4 did not suppress the cytotoxic capability of previously activated LAK cells. rIL4 directly suppressed rIL2-induced activation of precursors into LAK cells, since it inhibited both rIL2-induced proliferation and LAK cell activity in LGL-enriched cell fractions or in purified CD16+ NK cells. Suppressive effects of rIL4 were overcome by adding rIFN gamma to the culture. These results suggest that rIL4 is a potent inhibitor of rIL2-induced activation of PBL, and that the net LAK response in the host may be a function of the production of IL-2, IL-4 and rIFN gamma.