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Celtis sp. (commonly known as “hackberry”) fruits were collected from 101 North American sites located in 13 states and one Canadian province between the years of 1979–1994. The biomineralized carbonate endocarp of the hackberry, which is a common botanical fossil found throughout the Quaternary sediments of the Great Plains, was analyzed for its δ18O value and plotted against the δ18O value of site environmental water to demonstrate the potential of the hackberry as a paleoclimate indicator. This correlation was reinforced by intensive studies on extracted tissue-water δ18O value and hackberry endocarp carbonate δ18O value from three trees in Sterling, Colorado. The observed correlation in the large data set between hackberry endocarp carbonate δ18O value and environmental water is [endocarp δ18O=38.56+0.69×environmental water δ18O] (R=0.88; R2=0.78; p value<0.0001). The relation of the hackberry carbonate to temperature in the Great Plains was the following: (average daily-maximum growing season temperature [°C])=6.33+0.67 (δ18O of endocarp carbonate) (R=0.73; R2=0.54; p value=0.0133). The δ18O value of early Holocene fossil hackberry carbonate in the Pintwater Cave, southern Nevada, suggested precipitation δ18O values more positive than today (∼−4‰ early Holocene vs ∼−9 to −10‰ today). This shift, combined with paleobotanical data, suggests an influx of summer monsoonal moisture to this region in the early Holocene. Alternatively, the more positive δ18O values could be viewed as suggestive of warmer temperatures, although the direct use of Great Plains hackberry/temperature relationships to the Great Basin is of debatable value.