Increasing susceptibility to infectious and autoimmune phenomena have long been recognized to accompany advancing age in otherwise healthy individuals. Recently animal models of aging have suggested that age-associated immune dysfunction may correlate with defects in T cell apoptosis. We have examined activation-induced apoptosis defects in human peripheral T cells from young individuals (mean age = 31 ± 3 years old) compared to aged individuals (mean age = 67 ± 8 years old). Following in vitro activation of T cells with PHA and IL-2, apoptosis was measured in T cell subsets using 7-amino actinomycin D (7-AAD) staining and analysis via three colour flow cytometry. There was no significant difference in apoptosis of the total CD3+ T cell population at early and late time points. Interestingly, increased apoptosis in the CD3+ CD45RO- T cell population of older adults was observed by culture day 6. While the total number of CD3+ CD45RO- cells was not different between young (< 33 years) and old (> 65 years) individuals, 32% of these cells did not undergo apoptosis in younger individuals while only 10% of these cells avoided this fate in older individuals. These results suggest that accumulation of CD45RO+ T cells may occur in aged subjects due in part to preferential elimination of CD45RO- cells with activation. Furthermore, as new or continued immune response requires differentiation of CD45RA+ T cells to CD45RO+ T cells after activation, increased apoptosis instead of survival in aged individuals could lead to observed T cell immune deficiency.