During the later stages of the development of scrapie, an enhanced synthesis of DNA is detectable in the brains of affected mice. The synthesized DNA is largely confined to the nuclear fraction of the cell whereas the agent is mainly associated with mitochondria. There is evidence that the synthesis of the scrapie-associated DNA can be depressed in vivo in the presence of some specific inhibitors of DNA synthesis. An unsuccessful attempt was made to interfere with the normal development of scrapie by the repeated injection of inhibitors throughout the incubation period of the disease. It seems that the synthesis of DNA is not primarily involved in the development of the disease.