The transmissible agents of the spongiform encephalopathies are relatively resistant to inactivation, and accidental transmission has occurred in animals and man. Rigorous chemical or physical procedures are required to achieve decontamination, and their effectiveness can only be determined by bioassay in animals. The best-defined model is scrapie in mice or hamsters, and this has been used in many of the studies to establish practical inactivation procedures. Although a number of techniques had been considered to be effective, more recent observations suggest that some of these may not always be completely reliable. Research continues on scrapie inactivation, and work is in progress to extend this knowledge to the BSE agent.