With the use of increasingly sensitive methods for detection of the abnormal isoform of prion protein (PrP(Sc)) and infectivity in prion diseases, it has recently been shown that parts of the peripheral nervous system (PNS) of bovine spongiform encephalopathy (BSE)-affected cattle may become infected. It has been reported that prions spread to the central nervous system (CNS) via the PNS in sheep scrapie, but the pathogenesis of BSE in cattle is less well understood. To determine whether parts of the PNS other than those implicated directly in the hypothetical pathogenetic spread of agent from the intestine to the CNS become involved before or after the CNS is affected, PrP(Sc) distribution was investigated by a highly sensitive Western blotting technique in dorsal root ganglia, stellate ganglion, phrenic, radial and sciatic nerves, adrenal gland and CNS of cattle that were inoculated orally with BSE-affected brain and culled sequentially. In experimentally BSE-affected cattle, PrP(Sc) was first detected in the CNS and dorsal root ganglia; subsequently, PrP(Sc) accumulation was detected in the peripheral nerve trunks. PrP(Sc) was also detected in the adrenal glands of cattle that showed clinical signs. No PrP(Sc) was detected in the PNS of BSE-negative cattle. This study shows that, with respect to dorsal root ganglia, a paravertebral sympathetic ganglion and the somatic nerves examined, PrP(Sc) is detected in the PNS during the disease course at the same time as, or after, it accumulates in the CNS.