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 (²⁰⁶Pb/²⁰⁴Pb=17.169–18.021, ²⁰⁷Pb/²⁰⁴Pb=15.341–15.499, ²⁰⁸Pb/²⁰⁴Pb=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 (²⁰⁶Pb/²⁰⁴Pb=17.375–19.418, ²⁰⁷Pb/²⁰⁴Pb=15.361–15.519, ²⁰⁸Pb/²⁰⁴Pb=36.856–37.241) from the steep slope defined by the massive sulfide deposits in the Wales Group. In comparison, the Pb-isotopic ratios of Devonian polymetallic (Pb-Zn-Au-Ag) quartz-sulfide veins vary widely ( ²⁰⁶Pb/²⁰⁴Pb=18.339–18.946, ²⁰⁷Pb/²⁰⁴Pb=15.447–15.561, ²⁰⁸Pb/²⁰⁴Pb=37.358–38.354), straddling the slope defined by the massive sulfide deposits in the Moira Sound unit. The general decrease in ²⁰⁷Pb/²⁰⁴Pb ratio in these deposits, relative to the average crustal Pb-evolution curve, suggests that the most likely lead sources were those associated with oceanic volcanic rocks. The massive sulfide deposits in the Wales Group may have resided within an intraoceanic tectonic setting where the mantle was the predominant contributor of metals. Some contribution from reworked arc material or recycled older, hydrothermally altered oceanic crust (including pelagic sediment) is also possible. Lead sources of the massive sulfide deposits in the Moira Sound unit also included an older source region, possibly a Late Proterozoic or Cambrian volcanosedimentary sequence and the massive sulfide deposits in the Wales Group. Preliminary regional comparison of the Pb-isotopic data indicates that the Greens Creek (Admiralty Island, Alaska) and Windy Craggy (northern British Columbia) deposits probably did not share a common lead source with the VMS deposits on Prince of Wales Island. Other sulfide occurrences on Admiralty Island are also more radiogenic than those on Prince of Wales Island. Large differences in ²⁰⁷Pb/²⁰⁴Pb ratio suggest that the lead in the VMS deposits in different parts of the Alexander terrane evolved from sources with heterogeneous U/Pb ratios, resulting from mixing of mantle and crustal components.