Abstract. Dysfunction of antioxidant enzymes caused by mercuric compounds is partially associated with substantial induction of oxidative stress. In the present study, changes in renal and hepatic enzyme activity of an antioxidant protein manganese superoxide dismutase (Mn-SOD) after exposure to mercuric chloride (HgCl2) were examined in ICR mice. Subcutaneous administration of HgCl2 (0.253mg/kg) resulted in a decrease in renal Mn-SOD activity in a dose-dependent manner, whereas the hepatic enzyme activity was unaffected following injection of HgCl2. Mercury accumulation in the kidney was drastically higher (3475 times) than that in the liver after HgCl2 administration. Examining interactions of purified Mn-SOD with HgCl2 indicated that mercury ions suppressed Mn-SOD activity by reduction of the native form. These results suggest that inorganic mercury can directly interact with murine Mn-SOD, resulting in decrease of the enzyme activity and that the HgCl2-mediated significant reduction of renal, but not hepatic, Mn-SOD activity in vivo appears to be associated with the tissue specificity for mercury accumulation.