One-gram samples from a pool of crude brain tissue from hamsters infected with the 263K strain of hamster-adapted scrapie agent were placed in covered quartz-glass crucibles and exposed for either 5 or 15 min to dry heat at temperatures ranging from 150 degrees C to 1,000 degrees C. Residual infectivity in the treated samples was assayed by the intracerebral inoculation of dilution series into healthy weanling hamsters, which were observed for 10 months; disease transmissions were verified by Western blot testing for proteinase-resistant protein in brains from clinically positive hamsters. Unheated control tissue contained 9.9 log(10)LD(50)/g tissue; after exposure to 150 degrees C, titers equaled or exceeded 6 log(10)LD(50)/g, and after exposure to 300 degrees C, titers equaled or exceeded 4 log(10)LD(50)/g. Exposure to 600 degrees C completely ashed the brain samples, which, when reconstituted with saline to their original weights, transmitted disease to 5 of 35 inoculated hamsters. No transmissions occurred after exposure to 1, 000 degrees C. These results suggest that an inorganic molecular template with a decomposition point near 600 degrees C is capable of nucleating the biological replication of the scrapie agent.