Antigen receptor stimulation of mature alpha beta T lymphocytes can lead either to proliferation or death. Programmed cell death, termed apoptosis, leads to the clonal deletion of both thymocytes and mature T cells that establishes tolerance. How a mature T cell selects between proliferation and death is not understood. Here I show that interleukin-2 (IL-2) is a critical determinant of the choice between these two fates. Both CD4+ and CD8+ T cells previously exposed to IL-2 undergo apoptosis after antigen-receptor stimulation. Antibody blockade of IL-2 but not IL-4 reverses the marked reduction of lymph node V beta 8+ T cells caused in mice by the bacterial superantigen Staphylococcus aureus enterotoxin B. IL-2 may thus participate in a feedback regulatory mechanism by predisposing mature T lymphocytes to apoptosis.