The relationship between the oxidative stress and inactivation of hepatic enzymes was examined in rats. An intake of lipid peroxidation products or pro-oxidative drugs provokes oxidative stress in the living body. Secondary peroxidation products of linoleic acid were administered orally, and the oxidative stress was evaluated by thiobarbituric acid (TBA) and haemoglobin-methylene blue (HMB) tests, and by the reduction in tocopherol level. A specific decrease in hepatic phosphoglucomutase activity was found following the oxidative stress caused by the dose with secondary products. Then, ten pro-oxidative drugs were administered intraperitoneally and the effects on the enzymatic activity were determined. Among the ten drugs, CCl4, alcohol, paraquat, phenobarbital, thiopental and methylcholanthrene caused the TBA values to increase, and the phosphoglucomutase activity to decrease, in the liver 24 h after the doses. It was attempted to clarify the inactivation mechanism by using parenchymal hepatocytes. When the cells were cultured in medium containing aldehydic products originating from lipid peroxidation, these aldehydes significantly suppressed the induction of phosphoglucomutase by dexamethasone as compared with the cells in aldehyde-free medium. We consider that aldehydes inhibit the hormonal induction of phosphoglucomutase in the rat liver.