Data are presented on the results of blood typing 56 American buffalo (Bison bison) with 66 different cattle blood-typing reagents. Evidence is presented which indicates that at least nine genetic systems of blood groups now recognized in cattle have their homologues in bison. These are the systems A, B, C, F-V, J, L, M, S, and Z. Comparisons are drawn between blood factors common to bison and cattle, and between the phenogroups in each of the systems of the two species. It is shown that most of the bison phenogroups and, by implication, their controlling alleles have closely similar or precise homologues in cattle. It is also shown that bison have soluble blood group substances serologically indistinguishable from the J and Oc properties of cattle. The same is true for the isohemolysins anti-J and anti-U1 and certain heterohemolysins which occur naturally in the two species. Certain differences between the two species, notably those encountered in typing the F-V and C systems, still persist and those differences are probably more extreme than any so far encountered in comparing various breeds of domestic cattle. Furthermore, there is a marked reduction of heterogeneity in bison blood groups as contrasted with cattle. This is particularly true in the B system. Nevertheless, there are many striking resemblances that outweigh the few differences. The over-all results indicate close taxonomic affinity of the two species. On the basis of the evidence on blood groups and on other observations mentioned in the introductory remarks of this report, further consideration should be given to the proposition that the American buffalo and domestic cattle deserve to be recognized as members of the same genus.