Abstract: Memory lymphocytes, arising from naïve lymphocytes after antigenic stimulation and being long‐lived, are the cellular basis for immunological memory. Recent studies of CD8 T cells suggest that generation of CD8 memory T cells requires the engagement of T cell antigen receptors (TCR) with antigen, yet the maintenance of CD8 memory T cells appears to be dependent on cytokines, such as IL‐15, independent of TCR. Although considerable progress has been made in understanding the molecular and cellular events of TCR‐induced differentiation and proliferation in the past decade, less is known about the mechanisms of IL‐15 action. From a kinetic and comparative analysis of the responses of memory phenotype CD8 T cells to IL‐15 and TCR stimulation in vitro, we found that IL‐15 and anti‐CD3 induce highly similar responses in memory phenotype CD8 T cells as measured by general gene expression profiles, synthesis of effector molecules (IFNγ, TNFβ, granzyme B and perforin), induction of cytotoxicity, and cellular proliferation. These findings indicate that IL‐15 is not only a growth factor but also an antigen‐independent activator for CD8 memory T cells.