The expression of CD45RA on CCR7- human CD8+ memory T cells is widely considered to be a marker of terminal differentiation. We studied the time course of CD45RA and CCR7 expression on human antitumoral cytotoxic T lymphocyte (CTL) clones and blood CD8+ T cells after antigenic stimulation. Our results indicate that CD45RA+ CCR7- CD8+ T cells are resting memory cells that, upon antigenic stimulation and during the next 10 days, proliferate, lose CD45RA, and transiently acquire CCR7. In the absence of further antigenic stimulation, they progressively re-express CD45RA and become CD45RA+ CCR7-. We conclude that the expression of CD45RA on these cells is indicative of the time elapsed since the last antigenic stimulation rather than the incapacity to proliferate or particularly high lytic potential. This concept leads to a reinterpretation of the significance of the presence of CD45RA+ CD8+ memory cells in patients affected by viral infections or by cancer.