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We analyzed entheseal change in 159 skeletons from Moundville and surrounding settlements using primary fibrocartilaginous attachments of the upper limbs. Risk of entheseal change did not differ bilaterally, suggesting a wide variety of activities were used to exploit a diverse ecosystem. Consistent with predictions, Mississippian (1000-1500 CE) agriculturalists experienced greater risk of entheseal change than did Late Woodland (500-900 CE) hunter-gatherers. Attachments used in arm flexion were most affected, while rotator cuff entheses remained consistent over time. A temporal increase in muscular changes in males in concert with faunal evidence for resurgence of larger game (e.g., deer) is consistent with continued reliance on hunting alongside domestication of maize. Among Mississippians, younger males appear to have been carrying out the most strenuous tasks, contrary to earlier studies that suggested a decline in male activities with domestication. Mound centers consistently experienced the greatest upper body changes, in spite of faunal and botanical data supporting provisioning of elites by outlying sites. Center males, respectively, experienced more than 26 and 12 times greater changes at elbow extensors and brachialis than those from outlying settlements, with a significant decline from young to middle age among adults. Center females experienced increased risk at biceps insertions and common extensors of the humeri - trends that disappeared with age. Overall findings suggest increased upper body demands and shifting sex and age-dependent divisions of labor with maize intensification, but trends across settlements point to significant status-related body size selection in center males, with fewer differences among females., (Copyright © 2012 Elsevier GmbH. All rights reserved.)