The resistance of the infectious agent of scrapie disease to sterilization at 100° or 121°C is reputed to be inconsistent with the structure of conventional viruses. However, in kinetic studies the majority of hamster scrapie strain 263K infectivity was (like that of previously characterized viruses) rapidly inactivated at temperatures of 100°C or greater. Small resistant subpopulations remained. Similar heat-resistant subpopulations were observed at 60°C for phage λ but only in the presence of brain homogenate. Brain homogenate may also confer stability to small subfractions of scrapie infectivity. Such refractory subpopulations cannot be used to make structural inferences that are properly obtained from the behavior of the majority population as revealed in the initial inactivation.