This paper summarizes the results of field and laboratory investigations, including whole-rock geochemistry and radiogenic isotopes, of outcrop and drill core samples from volcanogenic massive sulfide (VMS) deposits and associated metaigneous rocks in the Wood River area of the Bonnifield mining district, northern Alaska Range (see fig. 1 of Editors’ Preface and Overview). U-Pb zircon igneous crystallization ages from felsic rocks indicate a prolonged period of Late Devonian to Early Mississippian (373±3 to 357±4 million years before present, or Ma) magmatism. This magmatism occurred in a basinal setting along the ancient Pacific margin of North America. The siliceous and carbonaceous compositions of metasedimentary rocks, Precambrian model ages based on U-Pb dating of zircon and neodymium ages, and for some units, radiogenic neodymium isotopic compositions and whole-rock trace-element ratios similar to those of continental crust are evidence for this setting. Red Mountain (also known as Dry Creek) and WTF, two of the largest VMS deposits, are hosted in peralkaline metarhyolite of the Mystic Creek Member of the Totatlanika Schist. The Mystic Creek Member is distinctive in having high concentrations of high-field-strength elements (HFSE) and rare-earth elements (REE), indicative of formation in a within-plate (extensional) setting. Mystic Creek metarhyolite is associated with alkalic, within-plate basalt of the Chute Creek Member; neodymium isotopic data indicate an enriched mantle component for both members of this bimodal (rhyolite-basalt) suite. Anderson Mountain, the other significant VMS deposit, is hosted by the Wood River assemblage. Metaigneous rocks in the Wood River assemblage span a wide compositional range, including andesitic rocks, which are characteristic of arc volcanism. Our data suggest that the Mystic Creek Member likely formed in an extensional, back-arc basin that was associated with an outboard continental-margin volcanic arc that included rocks of the Wood River assemblage. We suggest that elevated HFSE and REE trace-element contents of metavolcanic rocks, whose major-element composition may have been altered, are an important prospecting tool for rocks of VMS deposit potential in east-central Alaska.