Lead isotope compositions of sphalerite, fluorite, barite and sparry dolomite in Mississippi Valley-type deposits of the southern Appalachians fall into four different isotopic groups. Most sphalerite forms two small clusters, whereas barite, fluorite, and sparry dolomite compositions are more scattered. These lead isotope compositions reflect the distribution of the deposits, which are hosted by two main palcoaquifers. Lower Cambrian clastic and carbonate rocks host the Austinville (Zn-Pb), Cartersville (Ba), Embreeville (Zn), and Doughtery (Zn) deposits, all of which fall in a cluster of lead isotope compositions near 207 Pb/ 204 Pb = 15.73 and 206 Pb/ 204 Pb = 19.45. Lower Ordovician carbonate rocks of the Knox Group host the Copper Ridge (Zn), Eve Mills (Zn), Greeneville-Fall Branch (Ba-F), Mascot-Jefferson City (Zn), Powell River (Zn-Pb), Russell-Tazewell (Ba-F), and Sweetwater (Ba-Zn-F) deposits, which have more complex compositions. Sphalerite from Mascot-Jefferson City, Eve Mills, Sweetwater, and Russell-Tazewell plots in a cluster around 207 Pb/ 204 Pb = 15.67 and 206 Pb/ 204 Pb = 19.0, whereas that from Copper Ridge plots in both clusters. Fluorite from Sweetwater falls on a long array in 207 Pb/ 204 Pb- 206 Pb/ 204 Pb space that has a two-stage age of 1.55 to 1.9 Ga for t 2 = 360 Ma, the previously published 87 Sr/ 86 Sr isochron age obtained for the Mascot-Jefferson City district. Barite and sparry dolomite compositions are relatively similar and have lower 207 Pb/ 204 Pb and 208 Pb/ 204 Pb ratios than most sphalerite and fluorite. The spatial distribution of lead isotope compositions indicates that there were at least two mineralizing solutions, represented by the two lead clusters; the upper cluster solution dominated the Lower Ordovician palcoaquifer whereas the lower cluster dominated the Lower Cambrian palcoaquifer; and that the two solutions mixed in most areas except the Mascot-Jefferson City district, where zinc mineralization is strongest. Although the specific sources of these leads cannot be determined from available data on possible source rocks, the two lead clusters probably came from relatively young, well-mixed sedimentary basins and the lead in the fluorite must have come from a source with an unusally high U/Th ratio such as phosphoritc. This study confirms that the isotopic composition of lead in southern Appalachian Mississippi Valley-type deposits differs significantly from that found in mid-continent deposits.