Mortality of two size classes (<35 and >35 mm) of eastern oysters Crassostrea virginica when exposed to combinations of low salinity (1, 2, 3, and 4) for extended periods (up to 30 days) at summer water temperatures typical of the Virginia Chesapeake Bay subestuaries was examined. A critical salinity-temperature combination of less than two at greater than 28°C for more than 1 wk exposure for oyster mortality is suggested. A review of limited historical salinity-temperature tolerance data suggest selection of local populations of oysters having differing salinity tolerances. Such selection may prove critical to persistence of low-salinity populations in the Chesapeake Bay subestuaries with projected climate change.