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Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE or prion disease) which is readily transmissible to sheep by experimental infection and animals of ARQ/ARQ PRNP genotype (at codons 136, 154 and 171) have the shortest incubation period. Because it is possible that sheep in the UK could have been infected with BSE via feeding of contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection however this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages ( approximately 24 hours, 2-3 weeks, 3 months, 6 months) and adult sheep. The incidence of clinical BSE disease was high when unweaned lambs ( approximately 24 hours and 2-3 weeks) were inoculated but older weaned animals were much less susceptible. Incubation period was also found to be influenced by genotype at codon 141 of the PRNP gene as LF heterozygotes had a longer mean incubation period than either homozygote. The results suggest that UK sheep would have been at high risk of BSE infection only if contaminated supplementary foodstuffs had inadvertently been ingested by neonatal animals.