Aging leads to a decline in the reactivity of CD4 T cells, in humans and mice. However, we have reported that not all CD4 T cells in aged mice were hyporesponsive, that is, a particular subset maintained the ability to mount a normal response. In this study, we examined the possibility of recalling reactivity in the hyporesponsive CD4 T cell-subset in aged mice. In vivo experiments revealed the changes in CD4 T cell-subsets in aged mice to be antigen-independent and aging-dependent. Once the CD4 T cells became hyporesponsive, they persistently exhibited a weak response. Furthermore, immunization with a co-stimulatory antibody had no effect on T cell-responses in aged mice, although it had a significant effect in young mice. As this hyporesponsive subset accounts for the majority of CD4 T cells in aged mice, it is important to elucidate the cause of the hyporesponsiveness.