Effects of cadmium on hepatic glutathione (GSH) metabolism were characterized in a human-derived hepatoma cell line, Hep G2 cells. Intracellular GSH concentrations were significantly increased after incubation with cadmium at 5 and 10 microM for 24 and 48 hr. The rate of resynthesis of GSH after depleting cellular GSH by 0.5 mM of diethylmaleate was higher in cadmium (5 microM)-pretreated cells than that in untreated controls. GSH efflux from cadmium-pretreated cells was two-fold higher than that in untreated controls. On the other hand, incubation with cadmium at 5 and 10 microM for 60 min did not decrease GSH efflux. These findings suggest that increased intracellular GSH concentrations are attributed to enhanced synthesis of GSH under cadmium exposure, although the possibility of decreased intracellular consumption of GSH should further to be studied.