Age related immune disfunctions are the result of humoral and cellular changes of the immune system and reflect major alterations of T cell subpopulations which concern cyclic nucleotides and their precursors. There are now many reports showing that adenosine can affect some phenotypic and functional lymphocyte characteristics. We have found that a short preincubation (30') with adenosine can inhibit proliferative responses of peripheral blood lymphocytes to polyclonal mitogen Concanavalin A in young healthy controls (p less than 0.05) but not in aged healthy subjects. These data led us to the hypothesis that an impairment of the adenosine-adenosinedeaminase system could play an important role in the age-associated decline of immune responses. Our results show a highly significant reduction (16.45 +/- 3.56 vs 24.42 +/- 9.5 p less than 0.001) of adenosinedeaminase activity in peripheral lymphocytes of aged humans (mean age 75.5 +/- 6.7 range 23-30). Preliminary studies suggest that this alteration could be responsible to some extent, for the decreased mitogenic response of lymphocytes reported in ageing.