Stable isotopic ratios of carbon and oxygen (δ¹³C and δ¹⁸O) from mollusk shells reflect the water quality characteristics of Florida Bay and can be used to characterize the great temporal variability of the bay. Values of δ¹⁸O are directly influenced by temperature and evaporation and may be related to salinity, δ¹³C values of δ¹³C are sensitive to organic and inorganic sources of carbon and are influenced by productivity. Analyses of eight mollusk species from five short-core localities across Florida Bay show large ranges in the values of δ¹³C and δ¹⁸O, and reflect the variation of the bay over decades. Samples from southwester Florida Bay have distinct δ¹³C values relative to samples collected in northeastern Florida Bay, and intermediate localities have intermediate values.¹³C values of δ¹³C grade from marine in the southwest bay to more estuarine in the northeast. Long cores (>1m), with excellent chronologies were analyzed from central and eastern Florida Bay. Preliminary analyses ofBrachiodontes exustus andTransenella spp. from the cores showed that both δ¹³C and δ¹⁸O changed during the first part of the twentieth century. After a century of relative stability during the 1800s, δ¹³C decreased between about 1910 and 1940, then stabilized at these new values for the next five decades. The magnitude of the reduction in δ¹³C values increased toward the northeast. Using a carbon budget model, reduced δ¹³C values are interpreted as resulting from decreased circulation in the bay, probably associated with decreased freshwater flow into the Bay. Mollusk shell δ¹⁸O values display several negative excursions during the 1800s, suggesting that the bay was less evaporitic than during the twentieth century. The isotope records indicate a fundamental change took place in Florida Bay circulation early in the twentieth century. The timing of the change links it to railroad building and early drainage efforts in South Florida rather than to flood control and water management measures initiated after World War II.