CD8+ CD28- T cell clonal expansions frequently occur in elderly persons who fail to produce specific antibodies following immunization. These clones express effector cell markers and are mostly CD45RA+. When isolated and put into culture they are unable to proliferate, but produce IFNgamma upon stimulation. Many of the clones specifically recognize cytomegalovirus (CMV). These CD8+ type 1 effector cells seem to trigger a Th1 polarization, as CD4+ T cells from elderly persons without in vivo antibody production produce Th1, but only low amounts of Th2 cytokines upon stimulation with PHA. These results indicate that chronic latent viral infections may lead to the accumulation of terminally differentiated (senescent?) T cells. These cells have proinflammatory activity and seem to suppress humoral immune responses. This development may however be counteracted by the (genetic?) predisposition of an organism to support the generation and maintenance of a CD8+ IL-2/IL-4 producing CD25+ T cell population which occurs in 36 % of the persons > 60 years of age. These persons are still capable of raising a humoral immune response following immunization. Our data suggest that environmental as well as genetic influences affect the aging immune system. Their balance may be decisive for the maintenance of intact immune function in the elderly.