Age-associated alterations of hepatic cytosolic glutathione-S-transferase (GST) activities towards sulfobromophthalein sodium tetrahydrate (BSP), styrene oxide (STOX), trans-4-phenyl-3-butene-2-one (PBO), 1,2-dichloro-4-nitrobenzene (DCNB), and 1-chloro-2,4-dinitrobenzene (CDNB) were investigated in Fischer-344 rats of both sexes with ages ranging from 1.5 to 28 months. The GST activities towards PBO and DCNB in male rats increased with age till 6-12 months when maximum values were attained, and then gradually decreased till 28 months when the values became the lowest. The GST activities towards STOX and BSP did not show any significant increase after 1.5 months and stayed at this level till 12 months, followed by a gradual decrease till 28 months when the values were the lowest. In contrast, the GST activity towards CDNB in male rats did not show much of an age-associated alteration. Age-associated alterations in GST activities in females were much smaller than those observed in males. Sex differences in GST activities (significantly higher male values than female values) were observed with all the substrates examined at least at some time of the animal life. The kinetic studies of GST activities indicated that alterations in the relative abundance as well as the total quantity of GST isozymes caused the substrate selective alterations of GST activities with age.