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The Middle East is considered a climate change "hot spot", where rainfall is expected to decline in the upcoming decades due to Global Warming. Reconstructing the long-term natural climate variability of this region is critical for understanding and contextualizing the current hydroclimate change and enables evaluating potential mechanisms that govern it. Oxygen isotopes (δ18O) from cave deposits are a high-resolution paleohydrological proxy, which previously has been interpreted as direct measures of rainfall amount. However, cave δ18O is controlled by a series of processes (e.g., evaporation, condensation and rainout history), and therefore, any paleohydrological interpretation using cave δ18O requires a thorough understanding and quantification of the full hydrological cycle. In this paper, we use a simple Rayleigh distillation model to assess the various processes that govern the isotopic composition of precipitation and quantify changes in cloud distillation during the Holocene throughout the Middle East. The results show that a west-east isotopic distillation gradient persisted throughout the Holocene in the Middle East. The early Holocene, coeval with Sapropel 1, was characterized by high distillation and a large west-east distillation gradient. At the end of sapropel 1, distillation dropped and the west-east gradient declined. The middle to late Holocene was characterized by a gradual increase in distillation, however the west-east distillation gradient continued declining. Similarity between the late Holocene distillation reconstruction and the Dead Sea lake-levels, strengthens the reliability of cloud distillation as a suitable hydroclimate proxy. These results show that periods of high distillation in the Levant occurred during both high and low summer insolation (early and late Holocene, respectively), and thus, were most likely the result of two different climatic mechanisms. Our distillation and distillation gradient records provide a new way to characterize the long-term natural climate variability in the Middle East and thus help resolve the climatic mechanisms governing this variability. • Holocene cloud distillation quantified using cave δ18O in Middle East Caves. • High distillation and high continentality characterized Middle East Early Holocene. • High distillation and low continentality characterized Middle East Late Holocene. • Jeita Cave distillation is similar to Dead Sea levels throughout the Holocene. • Different climate mechanisms operated during the Early and Late Holocene. [ABSTRACT FROM AUTHOR]