In an attempt to determine whether scrapie infectivity can be found in the peripheral nervous system of a scrapie-diseased sheep, mice were inoculated intracerebrally or intraperitoneally with 10-fold dilutions of homogenates of Nervus (N.) axillaris, N. ulnaris, N. medianus, N. ischiadicus, N. tibialis, N. fibularis, and N.saphenus. Mice were observed for clinical signs of scrapie for 700 days and their brains were analyzed for accumulation of pathological prion protein by immunoblot. Substantial amounts of infectivity were found in all peripheral nerves tested except N.saphenus. Infectivity at titers of approximately 10(4.5) mouse infectious units (MIU)/g were detected in N. axillaris and N. ischiadicus, of approximately 10(3.0) MIU/g in N. ulnaris, N. medianus, N. tibialis, and N.fibularis, and of 10(6) MIU/g in the cerebellum. Since muscles are traversed by the nerve tracts tested, mutton of scrapie-diseased animals should not be regarded as being free of scrapie agent.