Salinities and homogenization temperatures of fluid inclusions in Mississippi Valley-type (MVT) deposits provide important insights into the regional hydrology of the Illinois basin/Reelfoot rift system in late Palaeozoic time. Although the thermal regime of this basin system has been plausibly explained, the origin of high salinities in the basin fluids remains enigmatic. Topographically driven flow appears to have been essential in forming these MVT districts, as well as many other districts worldwide. However, this type of flow is recharged by fresh water making it difficult to account for the high salinities of the mineralizing fluids over extended time periods. Results of numerical experiments carried out in this study provide a possible solution to the salinity problem presented by the MVT zinc-lead and fluorite districts at the margins of the basin system. Evaporative concentration of surface water and subsequent infiltration into the subsurface are proposed to account for large volumes of brine that are ultimately responsible for mineralization of these districts. This study demonstrates that under a range of geologically reasonable conditions, brine infiltration into an aquifer in the deep subsurface can coexist with topographically driven flow. Infiltration combined with regional flow and local magmatic heat sources in the Reelfoot rift explain the brine concentrations as well as the temperatures observed in the Southern Illinois and Upper Mississippi Valley districts.