Prion protein genes were sequenced in free-ranging Alaska caribou (Rangifer tarandus grantii). Caribou prion alleles are identical or nearly so to those of wapiti, white-tailed deer, and mule deer. Five single-nucleotide polymorphisms were detected with substitutions at residues 2 (V-->M), 129 (G-->S), 138 (S-->N), 146 (N-->N), and 169 (V-->M). The 138N codon had been previously reported only in prion pseudogenes of other cervids. In caribou, the 138S and 138N alleles are present at frequencies of approximately 0.7 and 0.3, respectively, and they are seen in both homozygotes and heterozygotes of three geographically separated herds, each a component of the continental metapopulation. Genetics seems to permit the spread of chronic wasting disease from middle-latitude deer to high-latitude caribou in North America.