Although the immunosuppressive properties of anti-CD3 mAbs are now widely recognized, we have accumulated data characterizing the T cell activating properties of these antibodies. While in some situations these activating properties may be viewed as unwanted side-effects (for instance OKT3-mediated T cell activation may be responsible for some of the first dose toxicity seen with patients receiving OKT3 for suppression of allograft rejection), we have shown that anti-CD3 mAb therapy can augment host immune responses and provide protection against some tumors and viral infections. Importantly, this augmented response allows the development of long term, specific immunity. Because the immunosuppressive and activating properties of anti-CD3 mAbs are so closely overlapping, we have sought to identify other agents that are capable of activating T cell subsets selectively. We have found that SEB activates T cell subsets selectively in vivo and that this activation can be exploited to prevent the outgrowth of a malignant murine tumor. Studies currently in progress, including phenotypic and functional analysis of TILs and in vivo T cell subset depletions, should result in a more precise understanding of how SEB-induced T cell activation inhibits tumor growth.