Declining immunity in aged individuals has been repeatedly verified. However, many of the studies have focused on functions not directly relevant to the antigens normally encountered in vivo. For example, although infectious agents represent a significant cause of morbidity and mortality in the elderly, age-related immune responses in such diseases have received very little experimental attention. The present study was, therefore, initiated to examine T cell-mediated immunity to influenza virus in aged mice. We observed that the primary cytotoxic T lymphocyte (CTL) response to influenza, which peaks at day 5 in young adult mice, is almost completely absent at that timepoint in aged mice. Our experiments indicate that the kinetics of the response are shifted, so that the maximum activity appears at days 7-9. Furthermore, a comparison of the peak responses of both age groups reveals a significantly lower magnitude in the aged mice. The diminished response was also observed for most of the old mice when antigenic stimulation occurred in vitro. Although the overall response was diminished, the characteristic T cell cross-reactivity for all A strain viruses was similar to that observed in young mice. The possible causes and consequences of the age-related decline in influenza-specific CTL activity are discussed.