Massive sulfide deposits of the southern Appalachians form two distinct groups of lead isotope ratios which correlate with their geologic settings. Piedmont massive sulfides are associated with volcanic rocks of predominantly Cambrian age. They have model lead ages which are too young, an effect of U/Pb enrichment of source rocks. Lead isotope ratios of Piedmont massive sulfide define a trend of decreasingly radiogenic values from the Mineral district, Virginia, to the Stone Hill deposit, Alabama, which probably reflects decreasingly ensialic volcanism from northeast to southwest. A regression through the data has a slope which corresponds to a secondary isochron age of about 3.7 b.y. The line is proposed to represent mixing between variable amounts of upper crustal lead (decreasing to the southwest) with lead from a source relatively depleted in U/Pb which has, however, experienced either continuous or episodic enrichment of uranium relative to lead. The occurrence of a similar trend in galenas from Kings Mountain belt ores is further evidence for such a source.Massive sulfides of the Blue Ridge geologic province occur in upper Precambrian metasedimentary sequences and are typically low in lead content. Lead isotope ratios of galenas from Ducktown and the Gossan Lead are highly enriched in 206 Pb compared to amounts expected for deposits of that age. The anomalously radiogenic component is probably the result of lead derived from the predominantly clastic sediments of the host sequences. The radiogenic component of the 206 Pb coupled with the narrow range of 207 Pb/ 204 Pb at Ducktown indicates that much older continental crustal rocks were not involved in the ore-forming process.Galenas from a vein in the Hamme tungsten district, North Carolina, form a tight grouping which is similar to lead in K-feldspars from postorogenic ( approximately 300-m.y.-old) granitic plutons. The mineralized veins of the Virginia gold pyrite belt have galenas with a wide spread of radiogenic lead isotope ratios and do not appear to be related to massive sulfide deposits of the central Virginia piedmont.