Polymorphisms within the prion protein (PrP) gene are associated with scrapie susceptibility. We analysed the PrP genes of 140 Romney Marsh sheep, the dominant breed in New Zealand, a country free from scrapie. We found PrP alleles that are associated with a high susceptibility to scrapie. Sheep with these PrP genotypes would probably succumb to scrapie when born and raised in a scrapie endemic environment. These findings correspond to those obtained in minor breeds from New Zealand. We conclude that scrapie development not only depends on host genetic factors but also requires exogenous factors. Our findings demonstrate the effectiveness of the measures taken by New Zealand to maintain free from scrapie.