We have evaluated the effects of dexamethasone (Dex) alone or in combination with interleukin (IL)-10 or transforming growth factor-beta 1 (TGF-beta 1) on human T cell proliferation. Both IL-10 and TGF-beta 1 significantly decreased the Dex concentration needed to inhibit T cell proliferation by 50% (IC50). Dex in combination with IL-10 completely inhibited T cell proliferation, even when IL-10 alone was ineffective, as in the case of phytohemagglutinin-induced T cell proliferation. The evaluation of the results according to the isobole method displayed a potent synergistic activity between Dex and IL-10, whereas the combination of Dex with TGF-beta 1 was additive. IL-10, but not TGF-beta 1, enhanced the inhibitory effect of Dex on IL-2 production. IL-2 and IL-4 only partly antagonized the antiproliferative effect of the combinations. IL-4 was as effective as IL-2 in antagonizing the combination of Dex with TGF-beta 1, but significantly less effective against the combination of Dex with IL-10. IL-10 and TGF-beta 1 are thus able to potentiate the Dex inhibitory effect on T cell proliferation and could be regarded as potential agents for future immunosuppressive protocols.