The damaging effect of perfusion of hydrophilic radical generating azo compound on the liver of normal and vitamin E-deficient rats and its inhibition by antioxidants were studied in order to increase understanding of the action of free radicals on biological tissues. The hepatic damage was evaluated from the release of cytosolic enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, mitochondrial oxidation metabolism and morphological change. Two kinds of hydrophilic azo compounds were used, one which decomposes spontaneously at a uniform rate to generate free radicals and the other which does not. The former induced hepatic damage in a dose-dependent manner, while the latter did not exert any damage. Both endogenous vitamin E in the membranes and a water soluble vitamin E analogue added simultaneously with a radical initiator suppressed the hepatic damage. These results show that the hepatic damage induced by perfusion of radical generating azo compound is caused not by the azo compound itself but by free radicals.