The "protein only" hypothesis holds that the infectious agent causing transmissible spongiform encephalopathies is a conformational isomer of PrP, a host protein that is predominantly expressed in the brain. This hypothesis is strongly supported by many lines of evidence. To date, prion diseases are unique among conformational diseases in that they are transmissible-experimentally and by natural routes (mainly by ingestion). The pathway of prions to the brain has been elucidated in outline. A striking feature of prions is their extraordinary resistance to conventional sterilization procedures and their capacity to bind to surfaces of metal and plastic without losing infectivity. This property, first observed in a clinical setting, is now being investigated in experimental settings, both in animals and in cell culture.