Heavy metal pollution can arise from many sources and damage many organisms. Exposure to the metal ions can leads to a reduction in cellular antioxidant enzyme activities and lowers cellular defense against oxidative stress. In this study we have tested effects of the some metal ions on the purified bovine kidney cortex glutathione reductase (GR). Cadmium (Cd2+), nickel (Ni2+), and zinc (Zn2+) showed inhibitory effect on the enzyme. The obtained IC50 values of Cd2+, Ni2+, and Zn2+ are 0.027, 0.8, and 1mM, respectively. Kinetic characterization of the inhibition is also investigated. Cd2+ inhibition is noncompetitive with respect to both oxidized glutathione (GSSG) (KiGSSG 0.060 +/- 0.005mM) and NADPH (KiNADPH 0.025 +/- 0.002mM). Ni2+ inhibition is noncompetitive with respect to GSSG (KiGSSG 0.329 +/- 0.016mM) and uncompetitive with respect to NADPH (KiNADPH 0.712 +/- 0.047mM). The effect of Zn2+ on GR activity is consistent with noncompetitive inhibition pattern when the varied substrate is the GSSG (KiGSSG 0.091 +/- 0.005mM) and the NADPH (KiNADPH 0.226 +/- 0.01mM), respectively. GR inhibition studies may be useful for understanding the mechanisms for oxidative damage associated with heavy metal toxicity.