SUMMARYPrevious studies have shown the association between the polymorphisms serine (S) or aspartic acid (D) at codon 146 of thePRNPgene and resistance to scrapie. All goats aged >12 months (a total of 1075 animals) from four herds with the highest prevalence of scrapie in the country were culled and tested, of which 234 (21·7%) were positive by either the rapid test or immunohistochemistry (IHC) for any of the tissues tested. The odds of scrapie infection occurring in NN146goats was 101 [95% credible interval (CrI) 19–2938] times higher than for non-NN146or unknown genotypes. IHC applied to lymphoreticular tissue produced the highest sensitivity (94%, 95% CrI 90–97). The presence of putatively resistant non-NN146alleles in the Cypriot goat population, severely affected by scrapie, provides a potential tool to reduce/eradicate scrapie provided that coordinated nationwide breeding programmes are implemented and maintained over time.