The potential suppressive effects of allospecific anergic T cells were investigated both in vitro and in vivo. Allospecific T cells were rendered unresponsive in vitro using immobilized anti-CD3 mAb. These anergic T cells profoundly inhibited proliferation of responsive T cells in an antigen-specific manner. The observed inhibition did not appear to be due to the release of inhibitory cytokines in that secretion of IL-2, IFN-gamma, IL-4, IL-10 and TGF-beta was greatly reduced following the induction of anergy, and neutralizing mAb specific for IL-4, IL-10 and TGF-beta failed to reverse the inhibition. Furthermore, the suppression mediated by anergic T cells required cell to cell contact. In vivo, adoptive transfer of anergic T cells into recipients of allogeneic skin grafts led to prolonged skin graft survival. Consistent with the lack of inhibitory cytokine production by the anergic cells, prolongation of skin allograft rejection was not influenced by the simultaneous administration of a neutralizing anti-IL-4 antibody. These results indicate that anergic T cells can function as antigen-specific suppressor cells both in vitro and in vivo.