Two prominent features associated with immunoseneseence are thymic involution and altered T-cell phenotype and responsiveness. We have shown previously that in CD2-fas transgenic mice, in which the Fas apoptosis molecule is constituatively expressed on T cells, T-cell senescence is greatly reduced. Using a different experimental approach, the relationship between T-cell senescence and apoptosis was analyzed on human PBMCs. The results indicate that there was increased apoptosis of CD45RO-(CD45RA+) T cells upon activation. We propose that this could account for the increase in CD45RO+ 'memory' T cells with aging in humans. Together these results are consistent with the notion that T-cell senescence is associated with altered apoptosis and decreased T-cell responsiveness. T-cell responsiveness remained high in CD2-fas transgenic aged mice, but there was no increase in overall life span of the mice. Increased T-cell responsiveness was associated with an increased acute-phase response and amyloid A deposition in the glomerulus of these mice. These data suggest that restoration of the T-cell immune function in aged individuals must be carried out in concert with correction of other immune factors that down modulate the acute-phase response to prevent undesirable side-effects.