The elevating effect of S-(1,2-dicarboxyethyl)glutathione (DCE-GS) esters on the glutathione (GSH) content was examined using human hepatocellular carcinoma cell line HepG2. The treatment with DCE-GS diester and triester (0.5 mM) increased the GSH level in HepG2 cells up to 145 and 175% over control level after 24h, respectively. DCE-GS diester and triester also elevated y-glutamylcysteine synthetase (y-GCS) activity in HepG2 cells up to 125 and 150% over the control level after 24h, respectively. However, this elevation of y-GCS did not occur on treatment with bis-(p-nitrophenyl)phosphate, non-specific esterase inhibitor. It is therefore concluded that DCE-GS diester and triester are transported into cells and hydrolyzed intracellularly to DCE-GS, and then DCE-GS produced promotes GSH synthesis due to the activation of y-GCS.