Observations and geochemical data provide insight into the paleohydrology influencing development of Mississippi Valley-type deposits in southeast Missouri and provide clarification and justification of flow paths in light of proposals of fault hydrodynamics versus a continuous aquifer model. Faults are recognized as pathways for, as well as horizontal barriers to, fluid flow in a hydrologically compartmentalized region. These relations also indicate that at least two geochemically distinct fluids mineralized Late Cambrian hosts and that these fluids had a similar history of progressive undersaturation with respect to galena.An overview of the synthesis indicates that one of the fluids may have originated in the Reelfoot rift, whereas the other evolved in a recharge area stretching along the Ouachita front and exploited the Reelfoot rift. Northwest-striking faults in the Precambrian basement acted as channels of discharge for flow out of or through the Reelfoot rift. Fluid movement along these pathways was rapid and allowed fluids to reach ore hosts during a migration interval related to the late Paleozoic Ouachita orogeny. Vertical circulation along faults and fracture systems introduced fluids into the existing Paleozoic section. Dispersion into the Lamotte Sandstone, resulting from relative permeability differences between discordant subvertical faults and the adjoining quartzarenite, was restricted to a northwest-trending, fault-bounded corridor and was concentrated at the base of the Bonneterre Formation. Continued vertical movement of fluids maintained fracture networks as vertical pathways, during the period that circulation localized Mississippi Valley-type deposits in the Late Cambrian section.