We studied the correlation between the in vitro lymphocyte proliferative response and some early parameters of lymphocyte activation in aged people. While a consistent number of elderly subjects showed significantly decreased proliferative responses to mitogen stimulation, interleukin-1 (IL-1) production and IL-2 receptor/DR antigen expression were comparable to those of young controls. The reduction in IL-2 production observed in some aged donors did not correlate with the decreased proliferative activity in response to mitogen. Moreover, addition to the cultures of recombinant IL-2 was not capable of restoring the proliferative response to normal levels. These data on the whole seem to argue against a primary involvement in age-associated lymphocyte hyporesponsiveness of an alteration in the early phases of lymphocyte activation engaging the complex lymphokine/receptor network.