Natural scrapie in sheep is associated with polymorphisms of the PrP g
ene, particularly at amino acid codons 136, 154 and 171. This paper re
ports the results of nine scrapie case-control studies in Bleu du Main
e, Herdwick, Merino x Shetland, Poll Dorset, Scottish Halfbred, Shetla
nd, Soay, Suffolk and Swaledale sheep from British flocks affected by
scrapie. In some outbreaks, scrapie was found to occur only in animals
with at least one PrP allele encoding valine at codon 136 (V-136), us
ually a relatively rare allele in healthy controls. In other outbreaks
, the V-136 PrP allele was either not found or was not an absolute pre
requisite for scrapie to develop. Although scrapie had a strong tenden
cy to affect sheep with PrP genotypes homozygous for glutamine at codo
n 171 (QQ(171)), these genotypes (QQ(171) but varying at other codon p
ositions) were relatively common in healthy controls. The reliable pre
diction of scrapie susceptibility in previously uninvestigated sheep p
ocks will therefore require information at least about mp genotypes at
codons 136 and 171.