The antiapoptotic protein Bcl-x(L) is induced in activated T lymphocytes upon costimulation through CD28, 4-1BB, and OX40. Bcl-x(L) is also highly enriched in memory T lymphocytes. Based on this body of evidence, it was thought that Bcl-x(L) plays an essential role in the generation of effector and memory T lymphocytes. We report that mice with a conditional deletion of Bcl-x in T lymphocytes develop a normal CD8(+) T cell response to Listeria monocytogenes infection. Furthermore, Bcl-x conditional knockout mice exhibit normal T-dependent humoral immune responses. These results indicate that Bcl-x is dispensable for the generation of effector and memory T lymphocytes and suggest that costimulation of T lymphocytes promotes their survival through a Bcl-x(L) independent mechanism.