The hydrogeology, distribution, and volume of saline water in 22 aquifers in the southern midcontinent of the United States were evaluated to provide information about saline groundwater resources that may be used to reduce dependency on freshwater resources. Those aquifers underlie six States in the southern midcontinent—Arkansas, Kansas, Louisiana, Missouri, Oklahoma, and Texas—and adjacent areas including all or parts of Alabama, Colorado, Florida, Illinois, Kentucky, Mississippi, Nebraska, New Mexico, South Dakota, Tennessee, and Wyoming and some offshore areas of the Gulf of Mexico. Saline waters of the aquifers were evaluated by defining salinity zones; digitizing data, primarily from the Regional Aquifer-System Analysis Program of the U.S. Geological Survey; and computing the volume of saline water in storage. The distribution of saline groundwater in the southern midcontinent is substantially affected by the hydrogeology and groundwater-flow systems of the aquifers. Many of the aquifers in the southern midcontinent are underlain by one or more aquifers, resulting in vertically stacked aquifers containing groundwaters of varying salinity. Saline groundwater is affected by past and present hydrogeologic conditions. Spatial variation of groundwater salinity in the southern midcontinent is controlled primarily by locations of recharge and discharge areas, groundwater-flow paths and residence time, mixing of freshwater and saline water, and interactions with aquifer rocks and sediments. The volume calculations made for the evaluated aquifers in the southern midcontinent indicate that about 39,900 million acre-feet (acre-ft) of saline water is in storage. About 21,600 million acre-ft of the water in storage is slightly to moderately saline (1,000–10,000 milligrams per liter [mg/L] dissolved solids), and about 18,300 million acre-ft is very saline (10,000–35,000 mg/L dissolved solids). The largest volumes of saline water are in the coastal lowlands (about 16,300 million acre-ft), Mississippi embayment and Texas coastal uplands (about 12,000 million acre-ft), and Great Plains (about 8,170 million acre-ft) aquifer systems. Of the 22 aquifers evaluated in this report, the Maha aquifer in the Great Plains aquifer system contains both the largest total volume of saline water (about 6,280 million acre-ft) and the largest volume of slightly to moderately saline water (about 5,150 million acre-ft).