This study was undertaken to assess the relation of Mississippi Valley-type mineralization to wall-rock alteration and brecciation in the Mascot-Jefferson City district, the largest part of the East Tennessee Mississippi Valley-type ore field. The main question of interest was whether the Mississippi Valley-type-forming brines created or greatly enlarged the breccia system that hosts the ore or whether the breccia system was a preexisting paleoaquifer that simply controlled movement of the mineralizing brines. A secondary, and closely related, question was whether brine-wall rock interaction deposited Mississippi Valley-type ore.The breccia system that hosts the East Tennessee ore field began as karst breccias which formed in the upper part of the Late Cambrian-Early Ordovician Knox Group during Middle Ordovician emergence. Brecciation, which was most common at the paleosurface and in a limestone-rich zone about 200 m below the surface, took place when limestone solution caused collapse of primary dolostone layers. Mississippi Valley-type mineralization, consisting of sphalerite and sparry dolomite, fills interstices in the breccias that formed in the limestone-rich part of the Knox Group. Ore is associated with "recrystalline dolomite" that replaced limestone and there is an inverse correlation between the original limestone and sphalerite abundance suggesting that the ore-forming fluids reacted strongly with limestone wall rock, possibly dissolving it where alteration was most intense.The assessment of a relation between alteration and Mississippi Valley-type mineralization was based on 3,533 surface drill holes covering the 110-km 2 Mascot-Jefferson City district, each of which provided stratigraphic data and quantified estimates of mineralization intensity and alteration intensity. These data show clearly that as much as 50 percent of the limestone in the mineralized breccia section was lost over enormous areas that extend far beyond significant mineralization. The intensity of this effect clearly decreases downdip (toward the east), away from the probable source of meteoric karst-forming waters. These relations, combined with isotopic analyses and reaction path calculations, suggest that breccia formation and limestone dissolution took place during the original karst breccia formation. In contrast, later Mississippi Valley-type mineralization was associated with replacement of limestone by recrystalline dolomite. The main effect of dolomitization on the chemistry of the Mississippi Valley-type brines, an increase in their Ca/Mg ratio, would not cause sulfide precipitation. Thus, it appears unlikely that Mississippi Valley-type-forming brines created much of their ore-hosting breccias or that water-rock interaction was a major cause of Mississippi Valley-type ore deposition.