The paper systematically deals with the background of regional isotopic compo-sitions in the lower and middle reaches of the Yangtze River and neighbouring areas. It isshown that the lead isotopic compositions of different geological formations and units are con-trolled by the primary mantle heterogeneity, dynamic process of crust-mantle interchange,abundances of uraninm, thorium and lead of various layers of the earth and timing. Studies onthe background of regional isotopic compositions may offer significant information forgeochemical regionalization, tracing of sources of ore-forming materials, and regionalprognosis of ore deposits.