In this study, plasma levels of both low-molecular-mass sulfhydryls/disulfides and mixed disulfides with proteins in 41 healthy humans aged 21-92 years were measured, with the aim of assessing whether there is a shift of the thiol/disulfide balance during aging and verifying some of the possible effects of the thiol imbalance. Our data suggest that aging is strictly correlated to a decrease in plasma glutathione and cysteinylglycine with the concomitant increase of most oxidized forms of thiols and a parallel increase in total cysteine and total homocysteine, probably due to an augmented efflux of these amino acids from various organs. The occurrence of two distinct regulatory systems for plasmatic pools of glutathione/cysteinylglycine on the one hand and cysteine/homocysteine on the other hand is hypothesized.