Prions are very resistant to inactivation, and accidental transmission has occurred through the use of inadequate decontamination procedures. Strong sodium hypochiorite solutions achieve inactivation but other chlorine-releasing compounds are less effective. 2M sodium hydroxide leads to substantial but incomplete inactivation; other chemical procedures such as the use of proprietary phenolic disinfectants are much less less effective. Infectivity can survive autoclaving at 132-138 degrees C, and under certain conditions the effectiveness of autoclaving actually declines as the temperature is increased. The small resistant subpopulations that survive autoclaving are not inactivated by simply re-autoclaving, and they acquire biological characteristics that differentiate them from the main population. Despite the limitations of autoclaving, combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective. Protein-fixation (e.g., by ethanol or formalin) substantially enhances the thermostability of these agents. This suggests that future successful inactivation strategies might best be developed by studying procedures that avoid protein-fixation.