We will continue the study of the pathogenesis of Creutzfeldt-Jakob disease, a subacute spongiform virus encephalopathy of man, in a timed experiment already in progress. The morphological findings will be correlated with the virological and neurochemical findings. Additional experiments in progress will follow to determine if there is a viremic stage in this disease. Sphingoglycolipid changes will be studied in order to find out whether a decrease in these components occurs concomitantly with morphological changes or can be shown prior to these changes. Fractionation and tissue culture studies will be initiated. BIBLIOGRAPHIC REFERENCES: Manuelidis, E.E., Angelo, J.N., Kim, J.H., and Manuelidis, L. Serial propagation of Creutzfeldt-Jakob disease in guinea pigs. Proc. Nat. Acad. Sci. (U.S.A.) 73:223-227, 1976. Yu, R.K. and Manuelidis, E.E. Gangliosides in guinea pig brains infected with Creutzfeldt-Jakob agent. (Abstract). Trans. Amer. Soc. Neurochem. (In press), 1976.