The Long‐Evans Cinnamon rat is a mutant strain that contracts hereditary hepatitis and, eventually, spontaneous hepatocellular carcinoma. Because we found a corresponding gross copper accumulation in the liver of the rats, we examined whether the development of hepatitis in our rat system could be prevented by administration of D‐penicillamine. D‐Penicillamine is a copper‐chelating agent and one of the drugs effective for human Wilson's disease, in which abnormal copper metabolism is also observed. The results show that D‐penicillamine treatment inhibited the elevation of serum transaminases, suppressed abnormal histological changes in the liver and completely prevented the onset of hepatitis in the Long‐Evans Cinnamon rats. We further found that the copper concentration in the liver and serum copper and ceruloplasmin levels were decreased, whereas the urinary copper level was increased in the D‐penicillamine—treated Long‐Evans Cinnamon rats. These findings demonstrate that the pathogenesis of hereditary hepatitis in Long‐Evans Cinnamon rats is due to abnormal copper accumulation in the liver. (HEPATOLOGY 1992;15:82–87).