Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Concerning these changes in T cell subpopulations, how much they depend on the immunogenetic background and how much they depend on individual antigenic load, such as chronic infections, should be assessed. As previously demonstrated in our population, the interleukin (IL)-2 high-producer genotype is less frequent in old men than in young people; conversely, the IL-10 high-producer genotype is increased in old men. In this study, we tried to assess the role of low- and high-producer genotypes for IL-10 and IL-2 in the CD4 and CD8 absolute values, taking into account gender and age. The results suggest that old men carrying an anti-inflammatory IL-10 high-producer genotype or a proinflammatory IL-2 low-producer genotype show the lowest values of CD8 cells. Although in our study we were not able to show any correlation with CD4 values and no functional assessment of T cell was performed, these results suggest that cytokine genotypes may be involved in the subpopulation dynamics in old age.