A large scale purification protocol employing zonal rotor centrifugation has been developed for scrapie prions. The extensively purified fractions derived using this protocol contained only one major protein, designated PrP, and rod-shaped particles. The rods measured 10 to 20 nm in diameter and 100 to 200 nm in length by negative staining; no other particles were consistently observed. SDS denaturation caused the rods to disappear, prion infectivity to diminish, and PrP to become sensitive to protease digestion. Arrays of prion rods ultrastructurally resembled purified amyloid and showed green birefringence by polarization microscopy after staining with Congo red dye. The rods appear to represent a polymeric form of the scrapie prion; each rod may contain as many as 1,000 PrP molecules. Our findings raise the possibility that the amyloid plaques observed in transmissible, degenerative neurological diseases might consist of prions.