The east Tennessee Mississippi Valley-type (MVT) ore field contains barite-fluorite and sphalerite deposits in a continuous paleoaquifer consisting of breccia zones in the Upper Cambrian-Lower Ordovician Knox Group. Paragenetic observations and fluid inclusion compositions in these deposits indicate that the Knox paleoaquifer was invaded first by Ca-rich brines (Ca:Na about 1) that deposited fluorite and barite, and later by Na-Ca brines (Ca:Na = 0.1 to 0.5) that deposited sphalerite. Geologic relations indicate that these brines were derived from the southeast, in the area of the Middle Ordovician Sevier foreland shale basin, and that membrane filtration could have played a role in enriching the early brines in Ca. Constraints imposed by fluorite solubility indicate further that all original connate water in the Sevier basin was required to deposit the estimated fluorite reserves of the ore field. Thus, the later, sphalerite-depositing brines represent recycled meteoric water from the Sevier basin or connate brines from underlying (Cambrian) shales.