The protective and antioxidative effects of 2(3)tert-butyl-4-hydroxyanisole (BHA) against cardiotoxicity and hepatotoxicity induced by doxorubicin in mice were investigated. After pretreatment with different oral doses of BHA, doxorubicin 30 mg.kg-1 was given i.p. Serum GPT, GOT, LDH and CK were determined, and the mortality rate of animals was observed. Quinone reductase (QR), glutathione-S-transferases (GSTs) and glutathione reductase (GR) were determined on tissue cytosols with enzyme dynamic methods. Malondialdehyde (MDA) was measured by the method of thiobarbituric acid. Compared with the doxorubicin group, the serum GPT, GOT, LDH, CK and the mortality rate of mice were significantly decreased by BHA pretreatment, and BHA was shown to inhibit the increase of MDA induced by doxorubicin (P < 0.01 and P < 0.0001). Administration of BHA resulted in increased activities of QR, GSTs and GR in the myocardium and liver (P < 0.05 or P < 0.0001). These results suggest that BHA has protective effect against the toxicity induced by doxorubicin via the induction of QR, GSTs and GR activities and anti-lipid peroxidation.