Mepacrine at 50 microM completely protected vitamin E-deficient rat erythrocytes from peroxidative hemolysis induced by dialuric acid or reduced glutathione under the standard experimental conditions. Malondialdehyde formation, which precedes the hemolysis, was also inhibited by mepacrine. These effects of mepacrine were observed when it was added after incubating the cells with dialuric acid before the malondialdehyde formation reached 50% of its maximal value. Mepacrine also inhibited NADPH-dependent lipid peroxidation in rat liver microsomes. The degree of inhibition by mepacrine of lipid peroxidation and hemolysis was dependent on the amount of red blood cells or microsomes in the reaction mixture.