The effects of gonadectomy and sex hormone replacement (either estradiol (E) or progesterone (P) or both (EP) in females, and testosterone (T) in males) on plasma and hepatic gamma-glutamyl transpeptidase (PGGT and MGGT respectively), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GRx) were investigated. 48 male and 72 female rats (120-150g each) were used. The male rats were divided into 4 groups: control, sham operated, castrated and castrated with testosterone replacement at a dose of 4mg kg(-1) body weight. The female rats were divided into 6 groups: control, sham operated and 4 groups which were gonadectomized, of which three groups received hormone replacements of estradiol (0.2 mg kg(-1) body weight), progesterone 4 mg kg(-1) body weight) and both estradiol and progesterone together. The animals were sacrificed after two and five months. Higher levels of GPx and GRx activities (p<0.01) were found in female rats whereas GST were higher in male rats. Although no differences were observed in PGGT activities between male and female rats, MGGT activities were higher in female rats at five months. Ovariectomy increased PGGT, GST and GRx activities and replacement with either E or P lowered the activities. Replacement with EP together brought the levels of plasma GGT, GST and GRx to that of intact females. Neither gonadectomy nor sex hormone replacement influenced hepatic GGT and GPx activities. Castration increased the hepatic GGT and GPx activities of male rats, but reduced the GST levels. Testosterone replacement brought the hepatic GGT and GPx activities to that of intact males. Castration and or testosterone replacement did not influence the levels of plasma GGT and GRx. The results suggest that GGT and GSH-related enzymes are subjected to modulation by male and female sex hormones.