Retinol-binding protein (RBP) is a specific transport protein which carries retinol in the circulation. RBP concentration in plasma and liver of rats following a large dose of acetaminophen (APAP) intraperitoneally was examined. The RBP concentration in plasma decreased significantly at 12 hr after the APAP administration, while the plasma albumin concentration was affected a little. Western blot and northern blot analyses showed marked changes in RBP but not in albumin. Thus, RBP was suggested to be more sensitive for the acute drug-induced hepatotoxicity than albumin. The decrease of RBP concentration in plasma was suggested to be caused by the dysfunction of RBP synthesis in the liver.