The stratigraphic record of climatic and palaeoceanographic changes in the Mediterranean during the late Messinian is controversial. On Sicily, sedimentary facies show a steady transgression, suggesting that sub-basins were hydrodynamically linked to a larger water body. Here we test this hypothesis using strontium isotope studies from Messinian materials collected from a range of sites in the Caltanissetta Basin of central Sicily. The strata include a regionally regressive ‘First Cycle’ of early-mid-Messinian age and a younger, transgressive ‘Second Cycle’. These cycles are separated by an inter-regional unconformity which may be correlated with base-level low stand in the Mediterranean. 87Sr/86Sr ratios for all First Cycle gypsum fall within the expected global marine composition (0.70891–0.70897). All Second Cycle analyses fall within a grouping of significantly lower values (0.70868–0.70878), a surprisingly tight but discrepant grouping for data collected from shells of a brackish water fauna and from gypsum. Analyses from these different Second Cycle materials are statistically indistinguishable. These results indicate that the strontium isotopic composition of waters from different sub-basins on Sicily are indistinguishable regardless of salinity during the late Messinian. Therefore these basins must have mixed with a larger, homogenized reservoir which we infer was the ancestral Mediterranean. Thus circum-Mediterranean basins may indeed chart regional palaeoceanographic and climatic events. By the end of Messinian times the base-level of the Mediterranean was within the range of the world's oceans but the water-body probably had a distinctly different but internally homogeneous strontium isotopic composition.