Although bovine spongiform encephalopathies (BSEs) have not been confirmed in Japan since 2009, atypical BSE, which may be a sporadic BSE, possibly occurs in future. To ensure safety of livestock products and byproducts, the generative and pathogenic mechanisms of BSE agents underlying prion diseases need to be clarified. We therefore perform in vitro experiments to elucidate condition necessary for prion formation and investigate generation process of variant prion. We comprehensively examine the following important issues of prion diseases: pathological changes, tissue distribution of prion, and biochemical and biological properties of prion generated in experimentally infected-animals. In addition to BSEs, scrapie in sheep and goats and chronic wasting disease (CWD) in deer and elk are also known. Typical and atypical scrapie have been identified in Japan, but occurrence of CWD has not yet been confirmed. Since these prion diseases are highly transmissible through contaminated bodily fluids or environment, we continue surveillance to monitor their occurrences and invasion from foreign countries strictly. In addition, we develop a rapid and sensitive method for prion detection which allows for safety assessment of feed. We further assess resistance to inactivation treatments and infectious risk to livestock and human of prions including CWD.