Technical Abstract: Chronic wasting disease is a transmissible spongiform encephalopathy of captive and free ranging mule deer, white-tailed deer, and elk in some areas of North America. Although the disorder in all three species is characterized by accumulation of the abnormal prion protein in the brain and lymph nodes of infected animals, prion gene variation among the species is different. In North American elk, a predisposing genotype has been described, with very low numbers of elk with the alternative genotypes succumbing to disease. In contrast, all mule deer genotypes appear to be affected. Analysis of the mule deer prion gene is complicated by the nearly universal presence of a cervid prion pseudogene, with a complete open reading frame contributing to the apparent heterogeneity observed when the open reading frame is amplified with primers that do not distinguish between the two forms of the gene. In white tailed deer, the pseudogene was observed in approximately 25% of the animals examined. The use of functional gene-specific primers demonstrated that white tailed deer of some genotypes are less likely to have disease than deer of alternative genotypes. The pseudogene was not associated with disease in this species. Diagnostic methods and genetic analysis of elk, white-tailed deer, and mule deer may need to be modified for each species.