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This study analyzes Pb isotopes combining biological (ancient human and prehistoric animal teeth) and geological (soil leachate, whole rock, and rock leachate) samples to determine the origins of prehistoric skeletal elements. It exemplifies how the biologically available Pb method assesses the early lifetime locations of ancient human populations using prehistoric animal teeth and the multivariate/linear nature of Pb isotope data. Lead isotopes provide a valuable technique, in part due to the correlation between their six stable isotope ratios. Other studies have used Pb isotopes for similar purposes, but no clear method for determining a local range has yet been formally defined and tested. The biologically available Pb method uses many prehistoric animal tooth enamel samples to establish a baseline for local ratios in the region, then compares their ratios’ linear patterning to human remains to test if they are non-local. The case study compares Pb isotopes from prehistoric animal teeth, human teeth, and whole rocks from southwest Arkansas. These results are compared to animal samples from Louisiana and Mississippi and human data from Illinois and New Mexico. Soil leachates, Pb concentrations of tooth enamel, and trace element analysis are used to assess contamination. Comparisons to southwest Arkansas whole rock Pb isotope ratios suggest they are too variable to be used for direct comparison to ancient human remains, illustrating that prehistoric animal teeth are more appropriate for direct comparison to prehistoric human teeth. The biologically available Pb method provides a key analysis tool needed for studies of ancient human sourcing.