We have previously reported the presence of Hsp60 and Hsp70 in the peripheral circulation of normal individuals. Given that the capacity to generate stress proteins declines with age, this study measured Hsp60 and Hsp70 levels in the sera of 60 individuals aged between 20 and 96 years. Levels of anti-human Hsp60, anti-human Hsp70 and anti-mycobacterial Hsp65 antibody were also measured. Senieur-approximated elderly subjects were well and randomly selected from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST). Samples from younger individuals were obtained from the Northern Ireland Blood Transfusion Service. Hsp60, anti-Hsp60, anti-Hsp70 and anti-mycobacterial Hsp65 antibodies were detected in all samples, whereas Hsp70 was detectable in only 46 of the samples analysed (77%). Regression analysis revealed a progressive decline in Hsp60 (759ng/ml < 40 years; 294ng/ml > or = 90 years) and Hsp70 (400ng/ml < 40 years; 20ng/ml > or = 90 years) levels with age whereas no relationship was apparent for anti-Hsp60 and Hsp65 antibody levels. Hsp70 antibody levels tended to increase with age (115U/ml < 40 years; 191U/ml > or = 90 years). This study in Senieur-approximated subjects demonstrates an apparent decrease in Hsp60 and Hsp70 with increasing age that does not appear to be related to anti-heat shock protein antibody status. These findings support in vitro work that demonstrates an age-related reduced ability to respond to stress. Further studies are required to understand the basis for declining serum Hsp60 and Hsp70 levels in aging and to elucidate their origin and role in the maintenance of homeostasis and resistance to environmental challenges.