The disease-associated prion protein (PrP Sc ) has been detected in the ileal Peyer's patches of lambs as early as one week after oral exposure to scrapie. In hamsters, the earliest reported time of PrP Sc detection in the Peyer's patches after oral exposure to scrapie is 69 days post-infection. To evaluate the acute uptake of inoculum and to investigate whether the Peyer's patches constitute the primary site of entry for scrapie after oral exposure, hamsters were each exposed orally to 1ml of a 10% brain homogenate from hamsters in the terminal stage of infection with the 263K strain of the scrapie agent. PrP Sc was demonstrated in the Peyer's patches only a few days after exposure, i.e., much earlier than previously reported. This study supports the view that the Peyer's patches constitute at least one of the primary entry sites of PrP Sc after oral exposure to scrapie.