Several different samples of scrapie-associated fibriIs (SAF) were extracted in identical fashion from the brains of golden Syrian hamsters infected with the 263K strain of scrapie agent and NIH Swiss mice infected with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) agent. Based on a total of over 500 measurements in individual fibrils in different extracts, hamster fibrils were more abundant, thicker and had better defined substructure than mouse fibrils. Hamster protofibrils were usually either twisted helically or in parallel arrays, whereas mouse protofibrils were often twisted, occasionally parallel, or could not be morphologically defined. Thus, SAF preparations from scrapie-affected hamsters can be uhrastructurally distinguished from those of CJD-affected mice, an observation that presumably reflects differences in their respective host-encoded amyloid protein subunits. © 1991, Academic Press Limited. All rights reserved.