The inhibitory effect of the dienone-phenolic triterpene, celastrol, on lipid peroxidation in rat liver mitochondrial membranes induced by ADP and Fe2+ was studied. The anti-peroxidative effect of celastrol was very strong: its 50% inhibitory concentration was 7 microM, and it was about 15 times more effective than alpha-tocopherol. Celastrol scavenged 1.5 molar equivalents of radicals in homogeneous aqueous ethanolic solution, whereas cysteine and alpha-tocopherol scavenged one and two molar equivalents of radicals, respectively. The process of anti-peroxidation of celastrol was biphasic, possibly due to stepwise inhibitions of peroxidation in the outer and inner mitochondrial membranes.