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Human population size in the Great Plains ecosystem before European contact has been of longstanding interest to scholars. The same is true of bison numbers. Given the near total dependence on bison by nonagricultural precontact humans, integrating information on both human and bison numbers from that time is of further interest, providing the focus for this paper. Recent research on the behavioral ecology of bison and related ungulates has led to the identification of two distinct, although not mutually exclusive, populations: resident and migrant herds. Moreover, migrants tend to vastly outnumber residents, often by more than 4 to 1. The best available evidence supports estimates of about 30 million bison in the Plains ecosystem during prehistoric and early historic times. Of these, about 6 million likely were nonmigrants at anyone time. These numbers provide a basis for estimating the numbers of human bison-hunters. We review four possible combinations of human use of resident and migratory bison populations and their implications for human numbers. Archaeological and historical information provides evidence that year-round use of residents, together with seasonal use of the more numerous migrants, was the most likely pattern of human usage of bison. Hence, we estimate the sustainable human bison hunting population to have been 86,000-130,000. This estimate is close to past population estimates based on direct counts and other extrapolations.