Bovine spongiform encephalopathy contamination of the human food chain most likely resulted from nervous system tissue in mechanically recovered meat used in the manufacture of processed meats. We spiked hot dogs with 263K hamster-adapted scrapie brain (10% wt/wt) to produce an infectivity level of ≈9 log10 mean lethal doses (LD50) per g of paste homogenate. Aliquots were subjected to short pressure pulses of 690, 1,000, and 1,200 MPa at running temperatures of 121–137°C. Western blots of PrPres were found to be useful indicators of infectivity levels, which at all tested pressures were significantly reduced as compared with untreated controls: from ≈103 LD50 per g at 690 MPa to ≈106 LD50 per g at 1,200 MPa. The application of commercially practical conditions of temperature and pressure could ensure the safety of processed meats from bovine spongiform encephalopathy contamination, and could also be used to study phase transitions of the prion protein from its normal to misfolded state.