The acquisition of long-term survival potential by activated T lymphocytes is essential to ensure the successful development of a memory population in the competitive environment of the lymphoid system. The factors that grant competitiveness for survival to primed T cells are poorly defined. We examined the role of IL-2 signals during priming of CD4(+) T cells in the induction of a long-lasting survival program. We show that Ag-induced cycling of CD4(+) IL-2(-/-) T cells is independent of IL-2 in vitro. However, IL-2(-/-) T cells failed to accumulate in large numbers and develop in effector cells when primed in the absence of IL-2. More importantly, Ag-activated IL-2(-/-) T cells were unable to survive for prolonged periods of time after adoptive transfer in unmanipulated, syngeneic mice. IL-2(-/-) T cells exposed to IL-2 signals during priming, however, acquired a robust and long-lasting survival advantage over cells that cycled in the absence of IL-2. Interestingly, this IL-2-induced survival program was required for long-term persistence of primed IL-2(-/-) T cells in an intact lymphoid compartment, but was unnecessary in a lymphopenic environment. Therefore, IL-2 enhances competitiveness for survival in CD4(+) T cells, thereby facilitating the development of a memory population.