The Altaid orogen was formed by aggregation of Paleozoic subduction-accretion complexes and Precambrian basement blocks between the Late Proterozoic and the Early Mesozoic. Because the Altaids are the site of abundant granitic plutonism and host some of the largest gold deposits in the world, understanding their formation has important implications on the comprehension of Phanerozoic crustal growth and metallogeny. In this study, we present the first extensive lead isotope data on magmatic and metasedimentary rocks as well as ore deposits of the southern part of the Altaids, including the Tien Shan (Tianshan) and southern Altay (Altai) orogenic belts. Our results show that each terrane investigated within the Tien Shan and southern Altay is characterized by a distinct Pb isotope signature and that there is a SW-NE Pb isotope gradient suggesting a progressive transition from a continental crust environment in the West (the Kyzylkum and Kokshaal segments of the Southern Tien Shan) to an almost 100% juvenile (MORB-type mantle-derived) crust environment in the East (Altay). The Pb isotope signatures of the studied ore deposits follow closely those of magmatic and metasedimentary rocks of the host terranes, thus supporting the validity of lead isotopes to discriminate terranes. Whereas this apparently suggests that no unique reservoir has been responsible for the huge gold concentration in this region, masking of a preferential Pb-poor Au-bearing reservoir by mixing with Pb-rich crustal reservoirs during the mineralizing events cannot be excluded.