The generation of memory T cells is critically important for rapid clearance and neutralization of pathogens encountered previously by the immune system. We have studied the kinetics of response and Ag dose requirements for proliferation and cytokine secretion of CD4+ memory T cells to examine whether there are qualitative changes which might lead to improved immunity. TCR Tg CD4+ T cells were primed in vitro and transferred into T cell-deficient hosts. After 6 or more weeks, the persisting T cells were exclusively small resting cells with a memory phenotype: CD44high CD62L+/- CD25-. Memory CD4 T cells showed a similar pattern of response as naive cells to peptide analogues with similar Ag dose requirements for IL-2 secretion. However, memory cells (derived from both Th2 and Th1 effectors) displayed faster kinetics of cytokine secretion, cell division, and proliferation, enhanced proliferation in response to low doses of Ag or peptide analogues, and production of IL-4, IL-5, and IFN-gamma. These results suggest there is a much more efficient response of CD4 memory T cells to Ag re-exposure and that the expanded functional capacity of memory cells will promote a rapid development of effector functions, providing more rapid and effective immunity.