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Diatom assemblages preserved in sediment cores from closed-basin lakes can provide high-resolution records of past hydrologic and climatic conditions, including long-term patterns in the intensity, duration, and frequency of droughts. At Moon Lake, a closed-basin lake in eastern North Dakota, a comparison of diatom-inferred salinity and the precipitation-based Bhalme-Mooley Drought Index (BMDI) over the last 100 years was highly significant, suggesting that the diatom record contains a sensitive archive of past climatic conditions. A sub-decadal record of inferred salinity for the past 2300 years indicates that extreme droughts of greater intensity than those during the 1930s “Dust Bowl” were more frequent prior to A.D. 1200. This high frequency of extreme droughts persisted for centuries and was most pronounced from A.D. 200–370, A.D. 700–850 and A.D. 1000–1200. A pronounced shift to generally wetter conditions with less severe droughts of shorter duration occurred at A.D. 1200. This abrupt change coincided with the end of the “Medieval Warm Period” (A.D. 1000–1200) and the onset of the “Little Ice Age” (A.D. 1300–1850).