As people age their ability to be successfully immunized by vaccination declines. We have found that the ability of naïve CD4 T cells to respond and develop into effector and memory cells declines markedly with age. To analyze the extent of the CD4 defect, we have used an adoptive transfer model so that we can focus on the defect in the naïve T cell population. We transfer T cell receptor transgenic naïve T cells from aged mice into young T depleted hosts and examine the response of the aged donor T cells compared young T cells. The responding aged naïve cells are slower to initiate division, expand less and make less IL-2 during their response in response to peptide and ALUM. They also provide little help to host B cells, resulting in dramatically reduced antibody. Ex vivo however, we find that addition of IL-2 or proinflammatory cytokines (IL-1, IL-6 and TNFalpha) can induce the aged naïve cells to become effectors and enhancement is also seen in vivo when inflammatory mix is added. Despite the restoration of effector generation, memory cells generated from "restored" aged effectors are poor producers of cytokines and do not proliferate well in response to recall stimulation. Importantly, if memory is generated from young naïve CD4 T cells and then evaluated after "aging", it is still intact. The defect in function of aged naïve cells is not seen in bone marrow-derived precursors of T cells and in fact aged precursors can develop into functional naïve CD4 T cells even in aged mice. This led us to postulate that the aging defect in the naïve cells may be a consequence of their post-thymic longevity. In support of this hypothesis, the aging defect develops more quickly when mice are thymectomized. We have found that as mice age, the rate of homeostatic division of naïve T cells increases. To test if such division contributes to the defect, we transfer young naïve T cells to hosts where they do or do not undergo such division and then evaluate their function. The cells that have recently divided, make less IL-2 and expand less when stimulated with antigen. This suggests that accumulated homeostatic division may cause some of the defects found in aged naïve T cells that are in turn in large part responsible for the poor vaccination efficiency in the aged.