Prion diseases are fatal neurodegenerative disorders that are caused by infectious agents known as prions. Prions are composed primarily of the pathogenic prion protein isoform, PrPSc. Because significant levels of infectivity have been detected in excrement from animals infected with scrapie and chronic wasting disease, studies on the dynamics of PrPSc levels in contaminated soil are needed to assess the possible horizontal transmission of prion diseases. Using protein misfolding cyclic amplification, we developed a sensitive detection method for scrapie PrPSc that is mixed with soil. Our detection method has the advantage of not requiring extraction of PrPSc from soil and could provide a sensitivity 1000 to 10,000 times higher than that obtained with an extraction-based method. In addition, we found that PrPSc levels in experimentally contaminated agricultural soils declined to different extents over the course of a 6-month incubation period. Our method appears to be a very useful technique for monitoring PrPSc levels in soil. (C) 2010 Elsevier Inc. All rights reserved.