The antioxidant activity of SB209995, a metabolite of carvedilol in human, was studied and compared with its parent compound, carvedilol. SB209995 or carvedilol inhibited iron-catalyzed lipid peroxidation assessed as thiobarbituric acid-reactive substance generated in brain homogenate with IC50s of 0.30 and 8.1 µmol/l, respectively. The oxidation of low-density lipoprotein (LDL) by macrophages or that initiated by Cu2+ ions was inhibited by SB209995 with IC50s of 59 nmol/l and 1.7 µmol/l, respectively. Under the same conditions, the IC50s of carvedilol were 3.8 and 17.1 µmol/l, respectively. Furthermore, SB209995 protected cultured endothelial cells against hydroxyl radical (OH) or superoxide (O–2)mediated lipid peroxidation and cytotoxicity, assessed as lactate dehydrogenase release and cell death. The results indicate that SB209995 is a more potent antioxidant than carvedilol and may contribute to the therapeutic effects of carvedilol.