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Locally extensive pre-Columbian human occupation and modification occurred in the forests of the central and eastern Amazon Basin, but whether comparable impacts extend westward and into the vast terra firme (interfluvial) zones, remains unclear. We analyzed soils from 55 sites across central and western Amazonia to assess the history of human occupation. Sparse occurrences of charcoal and the lack of phytoliths from agricultural and disturbance species in the soils during pre-Columbian times indicated that human impacts on interfluvial forests were small, infrequent, and highly localized. No human artifacts or modified soils were found at any site surveyed. Riverine bluff areas also appeared less heavily occupied and disturbed than similar settings elsewhere. Our data indicate that human impacts on Amazonian forests were heterogeneous across this vast landscape.