Cell stress responses are ubiquitous in all organisms and are characterized by the induced synthesis of heat shock proteins (Hsp). Previous studies as well as recent reports by our group have consistently suggested that aging leads to an increase in the basal levels of Hsp70. Here we extend these studies by examining the differential Hsp70 response of peripheral blood lymphocyte (PBL) subsets. It is well established that with aging, one of the major changes in the T cell pool is an expansion of T cells with the memory phenotype as well as those deficient for the CD28 molecule. To determine if alterations in the frequency of T cell subsets might be responsible for the observations, we have carried out a more comprehensive flow cytometric analysis of the various phenotypes of PBL under unstimulated conditions. Cells were obtained from 10 young and 10 elderly normal subjects. The basal Hsp70 levels in the various PBL phenotypes were comparable between young and elderly subjects. However, different patterns of Hsp70 response were noticed among the PBL subtypes, which were similar in both young and elderly subjects. In particular, the memory cell phenotypes produced more Hsp70 than the naïve phenotypes. These results suggest that aging-related changes in basal Hsp70 levels in PBL are linked to the altered frequency of lymphocyte subsets and not to increases in aged lymphocytes per se. In addition, the increase in Hsp70 can be interpreted as the result of a tendency towards more pronounced cellular differentiation in aging.