The Long-Evans cinnamon (LEC) rat, an animal model of Wilson's disease, develops hepatitis and liver cancer, Since LEC rats accumulate copper especially in the liver and since copper is a good catalyst of oxidation, selected plasma markers of oxidative stress in LEC rats and control Long-Evans agouti (LEA) rats were measured. Significant decrease in the plasma ascorbate level was observed even at the onset of hepatitis, suggesting that LEC rats are under oxidative stress because ascorbate is very susceptible to oxidation. The ratio of plasma ubiquinol-9, another oxidatively vulnerable antioxidant, to ubiquinone-9 in LEC rats also decreased significantly after the onset of hepatitis. Oxidative damage in the liver of LEC rats after the onset of hepatitis was also suggested by a decrease in the ratio of polyunsaturated fatty acids (PUFA) to free fatty acids (FFA) and an increase in the palmitoleic acid to FFA ratio in plasmas of LEC rats when compared with LEA rats since PUFA are vulnerable to oxidation and โฌ 9 desaturase is activated in order to compensate for the loss of PUFA. All of the above changes and hepatitis were prevented by adding a copper chelating agent, trientine dihydrochloride, to the drinking water of LEC rats. These data suggest that oxygen radicals may play an important role in the development of hepatitis and the subsequent liver cancer.