The mode of hepatorenal toxicity of acetaminophen (AAP) was compared between fructose-induced hyper-triglyceridemic and normal rats. The hypertriglyceridemic and normal rats received a single dose of AAP (0, 750 and 900 mg/kg ip) at week 5 of fructose-treatment. At 24 hrs after AAP-dosing, they were sacrificed and examined blood biochemically and histopathologically. Hepatotoxicity as indicated by an increase in plasma ALT and AST activities and centrilobular necrosis of hepatocytes was more severe in the normal rats than in the hypertriglyceridemic ones. In contrast, nephrotoxicity as indicated by an increase in plasma urea nitrogen content and necrosis of epithelial cells in the proximal straight tubules was more severe in the hypertriglyceridemic rats than in normal ones. Thus, in the fructose-induced hypertriglyceridemic rats, as compared with normal ones, hepatotoxicity of AAP became apparently less severe, whereas nephrotoxicity of AAP became significantly more severe.