Previous studies of peripherally injected mouse scrapie suggested that invasion of the CNS occurs initially in mid-thoracic cord by neural spread of infection from spleen and other visceral sites of extraneural replication. We now show that infection of the left sciatic nerve leads to direct spread of infection to brain (at a rate of approximately 1.0-2.0 mm/day), bypassing the need for extraneural replication and thus producing shorter incubation periods. However, the efficiency of intraneural infection is low. It can be increased by crush injury or by the injection of lysophosphatidyl choline, both of which temporarily increase the surface area of axolemma exposed to inoculum. Once infection is established, agent seems to spread throughout the nervous system but, at the clinical stage of disease, the titres in the PNS are much lower than in the CNS.