The replication of infectious agent has been studied in brain, thoracic cord, and lumbar cord of Compton white mice (Sinc87) infected with the 139A strain of scrapie. Nine experiments were carried out using four different peripheral routes of injection. A highly consistent pattern of results was obtained in which replication in the CNS started in the thoracic cord after about 35% of the total incubation period had elapsed (range 25 to 42%). This was followed by the simultaneous onset of replication in brain and lumbar cord which occurred 2 to 4 weeks later. It is difficult to explain these results on the basis of haematogenous spread of infection from peripheral sites of replication (e.g. in spleen) to the CNS. However, the data are consistent with spread of infection along peripheral nerves and, in particular, along nerves of the sympathetic nervous system. It is suggested, therefore, that this may be the major route by which scrapie agent invades the CNS.