Lipid composition was examined with cerebral cortices of three cases of Creutzfeldt-Jakob (C-J) disease and one case of subacute sclerosing panencephalitis (SSPE). Phosphatidylethanolamine decreased in both C-J and SSPE brains. Sphingomyelin increased in CJ. The levels of cholesterol esters which occurred in a trace amount in normal control were elevated in C-J and more severely in SSPE. The total amounts of gangliosides were reduced in C-J and SSPE. Gangliosides GD1b, GT1b and GQ1b in the biosynthetic pathway B [23] specifically decreased in C-J, while GM1 and GD3 increased. An increased content of GD3 may be related to the proliferation of reactive astrocytes. A decrease of 22:6 (n-3) accompanied with an increase of oleic acid in the fatty acid composition of the acidic phospholipid fraction was observed. This might be a cause for alterations in membrane function.