Compositions of δD, δ18O, 14C, and 3H are distinct in unconfined and confined groundwaters beneath the nonglaciated U.S. High Plains and reflect differences in average paleoclimatic conditions between the Holocene and the Middle to Late Wisconsinan. δD and δ18O are more depleted in confined groundwaters than in unconfined groundwaters beneath the southern and central Plains but are more enriched in confined than in unconfined groundwaters beneath the northern Plains. The range in stable isotopic composition of meteoric water north-to-south across the High Plains was apparently smaller during the Middle to Late Wisconsinan than it has been during the Holocene. The greater δD and δ18O depletion of confined groundwater beneath the southern and central Plains agrees with isotopic and noble gas data on other paleowaters that suggest Middle to Late Wisconsinan recharge temperatures were cooler than average Holocene temperatures by 5 to 8°C. The greater δD and δ18O enrichment of confined groundwater beneath the northern High Plains adds to previously reported evidence for stable isotope enrichment in glacial age precipitation across the northern Plains to the eastern United States. Additional research is needed to evaluate how patterns and mechanisms of moisture transport and other climatic variables might explain isotopic composition of paleorecharge during the last glacial period.