Despite general acceptance that immunologic changes are associated with aging and latent infection with Cytomegalovirus (CMV), no clear-cut distinction has so far been made between strictly age-related and CMV-induced changes. We therefore compared CD4+ and CD8+ naïve (CD45RA+CD28+), memory (CD45RA-CD28+), and effector (CD28-) T cells in CMV-positive (n = 164) and CMV-negative (n = 87) elderly persons and correlated CD8+ and CD4+ effector T cells with other T-cell subpopulations. Percentages of CD8+ as well as CD4+ effector T cells were higher, but percentages of naïve and memory cells were lower in CMV-positive compared to CMV-negative elderly persons. Negative correlations within CD8+ T-cell subsets were found to be present in both CMV-positive and CMV-negative elderly individuals. In contrast, correlations within CD4+ T-cell subpopulations and a positive correlation between CD8+ and CD4+ effector T cells were found in CMV-positive individuals only. Our results demonstrate that (a) in the elderly different T-cell subsets compete for space within the CD8+, but not the CD4+ T-cell population; (b) CMV induces changes in the CD4+ compartment that differ from the solely age-related changes seen in CMV-negative elderly population; and (c) the CMV-status of a population has to be taken into account before a conclusion on the effect of aging on the composition of the T-cell pool can be reached.