This study utilizes Pb isotope data to identify flow paths and Pb sources for Mississippi Valley-type ores in the midcontinent of the United States with emphasis on the Old and New Lead Belt subdistricts of southeast Missouri. Nearly 150 new analyses are reported which characterize the isotope systematics of both ore samples and Pb hosted by sedimentary rocks away from ore districts. A subset of the samples has been analyzed for sulfur isotopes. The nonore samples contain trace amounts of Pb largely hosted by trace metal- rich FeS 2 (termed "sulfide trace Pb"). These metal-rich sulfide phases are constrained by previous petrographic studies to have precipitated from the mineralizing fluids responsible for Mississippi Valley-type ore formation. Sampling was designed to evaluate the role of potential Cambrian and Ordovician aquifers as transport paths for Pb and S in an area broadly surrounding the locus of lead belt mineralization in southeast Missouri. Analyses are also presented for various leach fractions of rocks (termed "rock Pb") associated with these same potential aquifer units. Analyses of ore samples establish important benchmarks with which to compare the nonore samples. Ore samples were analyzed from southeast Missouri and include new data for both galena and nongalena phases (chalcopyrite, sphalerite, dolomite) from the New Lead belt subdistrict (Viburnum Trend subdistrict), and galena from the Old Lead Belt subdistrict and the outlying subdistricts of Annapolis and Indian Creek. Also studied were galena samples from the Central Missouri and Tri-State districts. The new data plus published values from the Northern Arkansas and Upper Mississippi Valley districts are nearly collinear on a uranogenic Pb isotope plot ( 206 Pb/ 204 Pb vs. 207 Pb/ 204 Pb). The slope of the linear regression line through this data is consistent with all the ores having been derived from the approximately 1450 Ma basement in the midcontinent area. However, the ores are very clearly separated on a plot of thorogenic isotope data ( 206 Pb/ 204 Pb vs. 208 Pb/ 204 Pb). Ores from either end of the Illinois basin, the Upper Mississippi Valley and Illinois-Kentucky fluorspar...