This project proposes to study slow infections caused by unconventional virus infections of animals (scrapie and transmissible mink encephalopathy) and man (kuru and Creutzfeldt-Jacob disease). The major emphasis is directed toward characterizing the physiochemical nature of the hamster-adapted scrapie agent using techniques of density gradient centrifugation, gel electrophosesis, radioisotope labeling, and RNA sequencing. Previous studies suggest that these unusual neuropathic agents represent a new form of self-replicating microorganism heretofore unrecognized by plant or animal virologists. Once these agents have been defined, it will be possible to examine mechanisms of replication and cell injury, and to compare viruses producing disease in animals with those which are pathogenic to man.