The Blue Ridge and Piedmont provinces of the Southern and Central Appalachians contain a series of massive sulfide deposits which are mined for copper, sulfur, iron with gold, and other by-products. The deposits at Ducktown, Tennessee, are the largest among them and one of the largest of this kind in the world. Eight tabular orebodies occur in the Ocoee metasediments of the Late Precambrian age more or less conformable to the enclosing host rocks. Orebodies are also surrounded by pronounced alteration zones with textures, mineralogy, and chemistry that distinguish them from the distant country rocks. Opinions regarding the origin of these massive sulfide deposits may be broadly classified as favoring either a metamorphic, a postmetamorphic hydrothermal, or syngenetic mode of formation.Rocks in the alteration zone are depleted in their delta 18 O values by approximately 2 per mil compared to the unaltered country rocks. Based on the average delta 18 O values, the following depletions are observed: quartz from 11.0 to 8.9, muscovite from 7.5 to 5.5, garnet from 7.0 to 4.7, biotite from 5.0 to 3.4, and calcite from 8.7 to 7.7 per mil SMOW. In the orebodies the average delta 18 O values are as follows: quartz = 9.5, calcite = 8.8, garnet = 4.7, and magnetite = 0.6 per mil SMOW. The delta 13 C values of calcite in the ore zone range from -13.4 to -17.4 and are similar to the values obtained in the alteration zone and the country rocks, which range from -15.2 to -20.2 per mil PDB. The minerals in the alteration zone and the country rocks show identical delta D values; -68 to -77 for biotite, -49 to -54 for muscovite, and -62 and -69 per mil SMOW for chlorite in the alteration zone.The quartz-magnetite isotopic temperatures in the orebodies range from 492 degrees to 541 degrees C and may be compared to the maximum quartz-biotite temperatures of 546 degrees C for the alteration zone and of 554 degrees C for the country rock. However, on the average slightly lower temperatures are observed in the alteration zone and the country rocks due to the effect of retrogression.The striking similarity of the delta 13 C and delta D values among the country rocks, the alteration zone, and the orebody suggests that the meteoric water recycled and maintained isotopic equilibrium with the metasediments and thus became metamorphogenic. In the ore zone a part of this water escaped through the shear zones during regional metamorphism and effectuated the alteration. The isotopic composition of this water was delta 18 O (sub H 2 O) = 5.4 to 7.0, delta D (sub H 2 O) = -33 to -36 per mil SMOW, and delta 13 C (sub CO 2 ) = -11.4 to -14.9 per mil PDB in the orebody and alteration zone and delta 18 O (sub H 2 O) = 7.2 to 8.5, delta D = -31 to -32 per mil SMOW, and delta 13 C (sub CO 2 ) = -12.7 to -16.7 per mil PDB in the distant country rock, assuming delta 13 C calcite nearly equal delta 13 C (sub Sigma C) . A preferential loss of CO 2 from the solutions is suggested as the process that probably caused the oxygen shift in the water. However, a magmatic water influencing the orebodies and the alteration zones cannot be totally ruled out.This isotopic study, along with the previously published ore fabric, sulfur isotope, and petrologic studies, indicates that the sulfides are partly pretectonic, probably syngenetic, and partly hydrothermal, formed by the remobilization of trace sedimentary sulfides and metals leached from the rocks during the period of regional metamorphism. The alteration around the orebodies took place in the descending stage of metamorphism as the influx of 18 O-depleted water through the shear zones continued.