The effect of gamma-glutamylcysteinylethyl ester (gamma-GCE), which is a precursor of reduced glutathione (GSH), on carbon tetrachloride (CCl4)-induced hepatic triglyceride (TG) accumulation in mice was investigated in comparison with that of GSH. Administration of gamma-GCE (160 micromol/kg), but not GSH (160 micromol/kg), to mice at 3 h after CCl4 injection (1 ml/kg, i.p.) significantly attenuated an increase in hepatic TG concentration at 6, 12, and 24 h after the CCl4 injection. A decrease in hepatic GSH concentration after the CCl4 injection was significantly diminished by the gamma-GCE administration, but not by the GSH administration. The correlation coefficient between hepatic TG concentration and hepatic GSH concentration was -0.627 (P < 0.001) when the results of all mice were grouped together. These results indicate that gamma-GCE can attenuate CCl4-induced hepatic TG accumulation in mice through the maintenance of hepatic GSH level.