Volcanogenic massive sulfide (VMS) deposits on Prince of Wales Island and vicinity in southeastern Alaska are associated with Late Proterozoic through Cambrian volcanosedimentary rocks of the Wales Group and with Ordovician through Early Silurian felsic volcanic rocks of the Moira Sound unit (new informal name). The massive sulfide deposits in the Wales Group include the Big Harbor, Copper City, Corbin, Keete Inlet, Khayyam, Ruby Tuesday, and Stumble-On deposits, and those in the Moira Sound unit include the Barrier Islands, Moira Copper, Niblack, and Nichols Bay deposits. Pb-isotopic signatures were determined on sulfide minerals (galena, pyrite, chalcopyrite, pyrrhotite, and sphalerite) to constrain metal sources of the massive sulfides and for comparison with data for other deposits in the region. Except for the Ruby Tuesday deposit, galena is relatively rare in most of these deposits. Pb-isotopic signatures distinguish the mainly Cu+Zn±Ag±Au massive sulfide deposits in the Wales Group from the Zn+Cu±Ag±Au massive sulfide deposits in the Moira Sound unit. Among the older group of deposits, the Khayyam deposit has the widest variation in Pb-isotopic ratios ( 206 Pb/ 204 Pb=17.169–18.021, 207 Pb/ 204 Pb=15.341–15.499, 208 Pb/ 204 Pb=36.546–37.817); data for the other massive sulfide deposits in the Wales Group overlap the isotopic variations in the Khayyam deposit. Pb-isotopic ratios for both groups of deposits are lower than those on the average crustal Pbevolution curve (µ=9.74), attesting to a large mantle influence in the Pb source. All the deposits show no evidence for Pb evolution primarily in the upper or lower continental crust. Samples from the younger group of deposits have scattered Pb-isotopic compositions and plot as a broad band on uranogenic and thorogenic Pb diagrams. Data for these deposits overlap the trend for massive sulfide deposits in the Wales Group but extend to significantly more radiogenic Pb-isotopic values. Pb-isotopic ratios of samples from the massive sulfide deposits in the Moira Sound unit plot on a different trend