Interleukin-4 (IL-4) is a cytokine difficult to induce in large quantities in freshly isolated cells. No malignant cell line has been described to date to produce IL-4 either constitutively or following activation. Here we report that HUT78 cells can be induced to produce IL-4 either by CD3 stimulation under cross-linking conditions or by soluble CD3 mAbs in the presence of PMA. IL-4-specific mRNA could be demonstrated readily under such conditions. Using this experimental model we investigated the role of IL-2 for IL-4 production. The addition of IL-2 strongly costimulated CD3-induced IL-4 production, whereas blockade of the IL-2/IL-2R pathway reduced IL-4 production by approximately 50%. IL-2 alone, however, could not induce IL-4 production. These results indicate that IL-2 is a helper of cytokine necessary, but not sufficient, for IL-4 production in HUT78 cells.