Lipids are an essential structural and functional component of cellular membranes. Changes in membrane lipid composition are known to affect the activities of many membraneassociated enzymes, endocytosis, exocytosis, membrane fusion and neurotransmitter uptake, and have been implicated in the pathophysiology of many neurodegenerative disorders. In the present study, we investigated changes in the lipid composition of membranes isolated from the cerebral cortex of rats treated with thioacetamide (TAA), a hepatotoxin that induces fulminant hepatic failure (FHF) and thereon hepatic encephalopathy (HE). HE refers to acute neuropsychiatric changes accompanying FHF. The estimation of membrane phospholipids, cholesterol and fatty acid content in cerebral cortex membranes from TAA-treated rats revealed a decrease in cholesterol, phosphatidylserine, sphingomyelin, a monounsaturated fatty acid, namely oleic acid, and the polyunsaturated fatty acids c-linolenic acid, decosa hexanoic acid and arachidonic acid compared with controls. Assessment of membrane fluidity with pyrene, 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene revealed a decrease in the annular membrane fluidity, whereas the global fluidity was unaffected. The level of the thiobarbituric acid reactive species marker for lipid peroxidation also increased in membranes from TAA-treated rats, thereby indicating the prevalence of oxidative stress. Results from the present study demonstrate gross alterations in cerebral cortical membrane lipid composition and fluidity during TAA-induced HE, and their possible implications in the pathogenesis of this condition are also discussed. Phospholipids together with cholesterol and glycolipids constitute 50-60% of the total cerebral membrane mass and provide for the stability, fluidity and permeability of neural membranes. Maintenance of the appropriate membrane lipid composition and fluidity are critical for the proper functioning of the integral membrane proteins, membrane bound enzymes, receptors and ion channels. Changes in the membrane cholesterol levels, polar head group of the glycerophospholipids, the length of the phospholipid acyl chain or in the degree of unsaturation alter the surface charge and physiochemical properties of membranes (Farooqui and Horrocks 1985). Such alterations have been observed during pathological changes associated with ischemia (Katsura et al. The glycerophospholipids in neural membranes are enriched in polyunsaturated fatty acids, acylated at the sn-2 position. These polyunsaturated fatty acids are involved in the determination of several physical properties of the membrane bilayer, such as phase transition, bilayer thickness and lateral domains. The high content of polyunsaturated fatty acids makes the neural membrane particularly susceptible to oxidative damage. The polyunsaturated fatty acids acylated at the sn-2 position of glycerophospholipids are susceptible to free-radical attack at the a-methylene group adjacent to the carbon-carbon...