Lead isotope compositions of sulfide minerals from Mississippi Valley-type deposits in Cambrian, Ordovician and Silurian rocks in the central Appalachians plot in distinct groups, one for each major district. Data for deposits in the Nittany Arch and Shawangunk districts form circular clusters, whereas data for the Timberville and Friedensville districts form more elongated fields. Comparison of these data to isotopic compositions of possible source rocks suggests that lead in the Nittany Arch, Shawangunk, and Timberville clusters came largely from Paleozoic igneous rocks or sediment derived from these rocks, whereas lead in the Friedensville deposits came from Grenville-age basement rocks. Additional lead from the Timberville district appears to have come from Triassic diabase, suggesting that as least some mineralization there is unusually young.These results contrast strongly with those for the southern Appalachians, where different Mississippi Valley-type districts have similar isotopic compositions over large areas. Only lead from the Ordovician-hosted Timberville deposits in the central Appalachians has an isotopic composition similar to that of any of the southern Appalachian deposits, and its composition is similar to that of deposits in the Lower Cambrian paleoaquifer of the southern Appalachians, rather than the Ordovician paleoaquifer. These relations indicate that although Mississippi Valley-type brines in the central Appalachians participated in significant cross-formational flow, they were not as regionally extensive as those in the southern Appalachians, a factor that might account for the relative scarcity of large Mississippi Valley-type deposits in the central Appalachians area.