In one subacute and two chronic cases of sclerosing panencephalitis (SSPE), the lipid composition and the fatty acid pattern of cerebrum were studied. The ganglioside concentration in the cerebral cortex was slightly to moderately decreased in the chronic cases. In all the cases there was an early and extensive loss of sphingolipids, especially of galactolipids, in the white matter. The fatty acid composition of the phosphoglycerides was only slightly changed from the normal. The cholesteryl esters contained very low concentrations of the polyenoic acids and thus differ completely from those of normal human brain. In cerebral white matter of the two chronic cases there was an almost complete disappearance of cerebrosides and sulfatides with long-chain fatty acids and a marked relative increase of those with medium-short acids and C23h.