Scrapie infectivity in the Hirt supernatant of a 20% scrapie-infected mouse brain filtrate was almost totally inactivated by pronase treatment. It was not affected by RNase A treatment and was only slightly reduced by DNase I treatment. These results indicate that a protein component is required for the transfection of scrapie nucleic acid and that free scrapie nucleic acid is either not infectious or its infectivity is extremely low.