The extraction and analysis of ancient and modern mtDNA has revitalized migration studies in North America. To test hypotheses of prehistoric population movement, the mtDNA haplogroups of 356 modern and 75 ancient individuals from Native American tribes throughout North America were determined. In addition, a subset of these samples was analyzed by sequencing a portion of the Control Region. The haplogroup frequency distribution of populations in the Northeast, Southwest, and Northwest all exhibit regional continuity and display inter-regional differences. In the Northeast the data supports both the Macro-Siouan hypothesis and a relatively recent intrusion of Northern Iroquoians into this region.; In the Southwest, Yumans and Pimans exhibit substantially greater genetic diversity than Jemez and Zuni probably due to admixture and genetic isolation, respectively. Southern Athapaskans likely experienced a bottleneck followed by extensive admixture during the migration to their current homeland in the Southwest. We find no evidence of movement of mtDNA lineages northward into the Southwest from Central Mexico, which, in combination with evidence from nuclear markers, suggests that the spread of Uto-Aztecan was facilitated by predominantly male migration.; Within the Northwest, frequency distributions for haplogroups A and B display a pattern of isolation by distance, with A decreasing and B increasing with distance from the Pacific Coast. The Chinook and Salish Plateau populations are similar to the Northwest Coast populations, and the ancient Vantage group is similar to the coastal Nuu-Chah-Nulth. While we do find evidence that the Western Idaho Archaic group is related to the population of the Hind site in Southern Ontario, neither of these populations is probably maternally related to modern Algonquians. Some evidence suggests that the homeland of modern Algonquians of eastern North America might be in the Okanogan Valley of the northern Columbia Plateau.
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