Lower Paleozoic strata in southeastern Kansas, southwestern Missouri and northern Oklahoma are predominantly marine carbonates that comprise portions of three regional flow systems. Groundwaters in these three adjacent systems exhibit extreme chemical and isotopic variations that delineate large-scale fluid mixing processes and two distinct mechanisms for the generation of saline fluids. Hydrodynamic and geochemical data closely correlate with geographic location and indicate that each system contains waters of markedly different origins. Results of elemental and isotopic mass balance modeling demonstrate that fluid mixing processes exert a fundamental control on groundwater compositions over the 40,000 km² study area. This quantification of groundwater mixing provides an important basis for determining endmember water compositions and evaluating hydrologic models for these flow systems. The three endmember groundwaters are as follows. 1) Dilute modern-day meteoric waters of the Ozark Plateaus aquifer system, recharged to southern Missouri. The evolution of this groundwater is dominated by interaction with host limestone and dolomite aquifer rocks. 2) Eastward migrating, saline Na-Ca-Cl groundwaters from the northern part of the Western Interior Plains aquifer system in central Kansas. These groundwaters are of meteoric origin with distant recharge areas. Salinity is acquired via the subsurface dissolution of Permian halite and subsequent water-rock interaction with silicate minerals. The chemical signature of these groundwaters, coupled with the presence of brines resulting from the dissolution of Permian halite in central Kansas, allow development of a model for the formation of saline Na-Ca-Cl fluids, a common component of many sedimentary basins. Additionally, the large-scale topographically driven flow of the northern part of this aquifer system is a modem analog for models of similar ancient systems. 3) Na-Ca-Cl brines in north-central Oklahoma. In contrast to the other saline endmember, the geochemical signature of endmember 3 groundwater, integrated with hydrogeologic data, indicate that this groundwater may represent a marine-derived brine from the deep Anadarko Basin. / text