Some people live in good health to great ages while others die relatively young, though we do not understand why this is so. However several studies show that longevity may be correlated with optimal functioning of the immune system. In fact, both longitudinal and cross-sectional studies performed in the last years have indicated that several functional markers of immune system may be used either as markers of successful ageing or conversely as markers of unsuccessful ageing. In these kinds of studies, the question that has to be asked is whether people live longer because of “good” immune function, or do they possess good immune function because other factors have enabled them to survive longer. Thus, to better understand the role of immune system in longevity, we have to search for immunogenetic markers of longevity. In fact, whether immune system plays a key role in the attainment of successful ageing, then genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Thus, these polymorphic genes could be markers of successful ageing or conversely of unsuccessful ageing. Further steps should include studies able to relate immunological and immunogenetic markers. For example, concerning the change in T cell subpopulations assessed as markers of unsuccessful ageing, the matter should be to assess how much these changes depend on the immunogenetic background and how much depend on the natural history of the individual, i.e. on an extra burden of antigenic load such as chronic infections. So we have analysed in our group of old and old oldest people, typed for IL-10 and IFN-gamma genotypes, previously demonstrated to be associated to longevity, the relationship between high or low producer genotypes and lymphocyte subpopulations. The results suggest that cytokine genotypes may be involved in the subpopulation dynamics in old age.