Transmissible spongiform encephalopathies are a group of infectious diseases typically associated with the accumulation of a protease-resistant and β-sheet-rich prion protein, PrPSc, in affected brains. PrP Sc is an altered isoform derived from the host-encoded glycoprotein, PrPC. The expression of PrPC is the highest in brain tissue, but it can also be detected at low levels in peripheral tissue. However, it is unclear whether a significant amount of PrPC is released into body fluid and excreted into urine. We have developed a simple, rapid method for the reliable detection of PrPC in urine from normal subjects by Western blotting. Our method can easily and reliably detect PrPC in apparently healthy individuals using less than 1 ml of urine in which the amount of urinary PrPC is estimated to be in the range of low micrograms/liter. Copyright © 2005 by the Society for Experimental Biology and Medicine.