The isotopic compositions of lead in copper-bearing hydrothermal sulphide deposits from the central-eastern Southalpine domain were analysed using a Multi-Collector-ICP-MS. The data were combined with existing lead isotope data (ore lead) for hydrothermal polymetallic deposits from the same area and compared with the isotopic compositions of potential lead sources. Copper and polymetallic pre-Variscan (Late Ordovician–Early Silurian) stratiform, post-Variscan (Permian to Triassic) vein, and stratabound sediment-hosted (Late Permian to Early Triassic) deposits, are characterised by highly variable ratios of radiogenic to non-radiogenic lead, but show very similar, high, time-integrated μ (=238U/204Pb) and W (=232Th/204Pb) values. A progressive relative increase in radiogenic lead is observed from (i) pre-Variscan deposits to (ii) post-Variscan sulphide-rich veins in the Variscan metamorphic basement and in the lower units of the Early Permian volcanic sequence, to (iii) post-Variscan sulphide-rich and fluorite-rich veins in the upper units of the Early Permian volcanic sequence, to (iv) post-Variscan fluorite-rich veins cutting the overlying Late Permian sediments and mid-Triassic mafic dikes. The dominant lead sources for all these deposits were Cambrian–Devonian (meta) sediments of the Variscan basement. Contributions from Permian and Triassic igneous rocks were of minor importance, if any, even for vein deposits which were evidently related to Permian magmatism. The isotopic compositions of some of the Permian vein deposits are consistent with, although they do not unequivocally prove, remobilization of metals from the pre-Variscan stratiform deposits. Stratabound deposits in the Late Permian sandstones and, possibly, those in the Early Triassic carbonates also received a major lead input from the Variscan metasediments, with a variable additional contribution from the host Permian sediments. Deposits in Triassic magmatic rocks are displaced to slightly lower μ and W values, suggesting lead contribution from Triassic magmatism. The high μ and W values of the deposits studied here are consistent with regional isotopic patterns of Pb–Zn-rich deposits in more northerly and easterly sectors of the Eastern Alps (Austroalpine, eastern Southalpine) and of several circum-Mediterranean Pb–Zn and polymetallic deposits of Paleozoic to Triassic age (Sardinia, Betic Cordillera) or derived from remobilisation of Paleozoic deposits (Tuscany). This isotopic uniformity suggests that an isotopic province characterized by the dominance of old (Early Proterozoic to Archean) detrital source material extended across a relatively wide portion of the former north-Gondwanan margin.