Regional depressurization due to groundwater withdrawal from a large confined midcontinent aquifer may cause significant changes in the regional flow field and solute distributions through time. This study addresses the effects of depressurization in the Silurian-Devonian carbonate aquifer in the western flank of the Appalachian Basin in Ohio, where salinity-derived variable-density flow effects are significant. This complex hydrogeologic environment is examined using an interpretative, transient, numerical flow and transport model to examine the hydrodynamics involved in the salinization process, to simulate changes in the velocity field and solute distributions over the past 100-year period, and to forecast the effects of three different depressurizing scenarios over the next 100-year period. The results indicate that large-scale depressurization can lead to significant changes in the regional flow patterns, resulting in changes in solute distributions and salinization of a portion of the aquifer. Depressurization creates vertical flow gradients within the carbonate aquifer that transport brine from underlying and overlying shale units into the updip freshwater portion of the aquifer. Model results show the development of flow reversals in the downdip portions of the aquifer that facilitate transport of brine from the deeper portions of the carbonate aquifer. These processes result in significant water quality degradation in the updip portion of the aquifer, which is extensively used for municipal, industrial, and domestic water supplies. Our results indicate the need to monitor water levels, pumping rates, and water quality so that future management decisions regarding the sustainability of the resource are based on complete and accurate field data. ¿ 2000 American Geophysical Union