In the confined Wilcox aquifer of southeast Missouri and northeast Arkansas, certain major and minor solutes show distinct trends along the regional hydraulic gradient, while concentrations of other solutes remain relatively constant. In particular, Na+ and Cl- tend to increase; Ca2+, Mg2+, K+, Fe, and SO42- tend to decrease; and HCO3-, Si, and dissolved organic C (DOC) are relatively constant. Using speciation calculations, saturation-index calculations, and inverse modeling in PHREEQC, we identified a combination of processes that are likely to control groundwater chemistry. These are: 1) dissolution of calcite; 2) reduction of goethite and oxidation of organic matter (as CH2O); 3) precipitation of siderite and pyrite; 4) release of Na+ in exchange for Ca2+, Mg2+ and K+ on clay mineral surfaces; and 5) diffusion of Cl- and SO42- from adjoining confining units containing connate water. By analogy with previous studies of regional aquifer systems in the Atlantic Coastal Plain, we hypothesize that dissolution of shell calcite occurs in the adjoining Claiborne Group. Organic matter exists as lignite in Wilcox and (or) Claiborne sediments; mole transfers of CH2O are larger for upgradient pairs of wells than for downgradient pairs. Goethite is inferred as a product of weathering of glauconite, which has been observed in Wilcox sediments along with pyrite. d13C of dissolved inorganic C ranged from -7.3 to -12.4, with no discernible trend along the flowpath. Pending further modeling, we deduce that these values represent mixing of enriched 13C from calcite and depleted 13C from organic matter.