© 2015, Springer-Verlag Berlin Heidelberg. Comprehension of the genesis of Pb-Zn ore systems is currently limited by a poor understanding of where these metals are sourced from. Our study of metal mobility during regional metamorphism in the Mt. Lofty Ranges, South Australia, demonstrates that in staurolite-absent siliciclastic metasedimentary rocks, biotite contains >80 % of the bulk rock Zn, as well as a considerable proportion of the total Pb. Fluid flow through these metasedimentary rocks led to a continuous depletion of Pb and Zn on a mineral and bulk rock scale during prograde regional metamorphism. We calculate that ∼80 % of the bulk rock Zn and ∼50 % of the bulk rock Pb were mobilised, mainly through reactions involving biotite. These reactions led to a calculated Pb and Zn “loss” of ∼2.7 and 27 Mt, respectively, in the high-grade metamorphic zone. Halogen contents of apatite and biotite and bulk rock Zn isotope data provide evidence that Cl-rich metamorphic fluids were important for metal transport. Hence, fluid flow accompanying prograde metamorphism of typical sedimentary rocks can mobilise base metals to the degree required to potentially supply significant Pb-Zn ore systems.