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Prions are novel proteinaceous-infectious agents that have been implicated in transmissible spongiform encephalopathies. It is now generally accepted that noninfectious prion proteins are normally produced by the host and may undergo a conformational change to an abnormal, pathologic form, which appears to be responsible for disease symptoms. Many methods of decontamination and sterilization are claimed to be ineffective against prion proteins. Incidences of iatrogenic transmission of prions due to medical devices have been reported, and the recommended clinical practices when handling suspected cases are reviewed. Recent results with a peracetic acid based sterilant indicate that it may be a safe and effective means of prion inactivation on medical devices.