Although the ultimate target of infection is the CNS, there is evidence that the peripheral nervous system (PNS) is involved in the pathogenesis of Transmissible Spongiform Encephalopathies (TSEs). We used immunocytochemistry to identify the presence of pathological accumulations of a host protein, PrP, in the CNS and PNS (sensory and autonomic ganglia) of hamsters orally infected with 263K scrapie. All hamsters showed pathological deposition of PrP in most brain areas, along the length of the spinal cord, in nodose (NG) and dorsal root (DRG) ganglia and in the coeliac mesenteric ganglion complex (CMGC). In one case, scant deposition was observed along a few axons of the vagus nerve. This finding suggests that, after oral challenge, TSE infectious agent uses neural pathways and ganglia of the peripheral nervous system to reach target sites in the CNS.