Volcanogenic massive sulfide deposits in the southernmost Appalachians of east-central Alabama and west-central Georgia are associated with metamorphosed submarine basalts and felsic rocks of the Ashland, Wedowee, and Talladega lithotectonic terranes. These three terranes lie between the Brevard fault on the south and the Talladega-Cartersville and Hayesville faults on the north. The oldest sulfide deposits occur in a regional setting characterized by a thick sequence of metamorphosed Eocambrian to lower Paleozoic continentally derived clastic and intercalated submarine metavolcanic rock. The metamorphosed clastic rocks represent the basal section of a rifted margin prism, whereas the metavolcanic rocks represent rhyolites, andesites, and basalts which were probably erupted along rift zones of a spreading back-arc basin. Most of the volcanogenie massive sulfide deposits are localized within metavolcanic rocks and are rare or absent in the enclosing or interbedded metasedimentary rock. The youngest sulfide deposits occur in the distal part of a volcanic arc sequence of the Talladega terrane, which terminated sediment deposition and volcanic activity in the region. Talladega terrane sulfide deposits appear anomalously young (Devonian) respective to other deposits in the eastern United States.Three types of massive sulfide host rock associations have been recognized in the southernmost Appalachians; Kuroko-type deposits associated with predominantly felsic volcanic assemblages, Anyox-type deposits associated with predominantly mafic volcanic assemblages, and Besshi-type deposits associated with interbedded assemblages of clastic sedimentary and mafic volcanic rocks.