T cell activation through the TCR can result in either cell proliferation or cell death. The role of costlmulatory receptors in regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 costimulation to augment the, production of IL-2, which acts as an extrinsic survival factor for T cells. In addition, CD28 costimulation augments the intrinsic ability of T cells to reslst apop tosis. Although CD28 signal transduction had no effect on Bcl-2 expression, CD28 costimulatlon was found to augment the expression of Bcl-xL substantially. Transfection experiments demonstrated that this level of Bcl-XL could prevent T cell death in response to TCR cross-linking, Fas cross-linking, or IL-2 withdrawal. These data suggest that an Important role of CD28 costimulation is to augment T cell survival during antigen activation.