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Sr isotope records from marginal marine basins track the mixing between seawater and local continental runoff, potentially recording the effects of sea level, tectonic, and climate forcing in marine fossils and sediments. Our 110 new Sr-87/Sr-86 analyses on oyster and foraminifera samples from six late Miocene stratigraphic sections in southern Turkey, Crete, and Sicily show that Sr-87/Sr-86 fell below global seawater values in the basins several million years before the Messinian Salinity Crisis, coinciding with tectonic uplift and basin shallowing. 87Sr/86Sr from more centrally located basins (away from the Mediterranean coast) drop below global seawater values only during the Messinian Salinity Crisis. In addition to this general trend, 55 new Sr-87/Sr-86 analyses from the astronomically tuned Lower Evaporites in the central Apennines (Italy) allow us to explore the effect of glacio-eustatic sea level and precipitation changes on Sr-87/Sr-86. Most variation in our data can be explained by changes in sea level, with greatest negative excursions from global seawater values occurring during relative sea level lowstands, which generally coincided with arid conditions in the Mediterranean realm. We suggest that this greater sensitivity to lowered sea level compared with higher runoff could relate to the inverse relationship between Sr concentration and river discharge. Variations in the residence time of groundwater within the karst terrain of the circum-Mediterranean region during arid and wet phases may help to explain the single (robust) occurrence of a negative excursion during a sea level highstand, but this explanation remains speculative without more detailed paleoclimatic data for the region.