The activation of pyrite by copper and lead ions is an important issue for the selective flotation of base metal sulfide minerals. In this study, the effect of electrochemical potential manipulated by reducing and oxidizing agents during grinding on the activation of pyrite by copper and lead ions was studied. Zeta potential measurements, X-ray photoelectron spectroscopy (XPS) and ethylene diamine tetraacetic acid (EDTA) extraction as well as copper and lead solution speciation simulations were used to correlate pyrite flotation with the surface properties of copper and lead-activated pyrite. The electrochemical potential during grinding had a significant effect on the activation of pyrite by copper ions, but little effect on the activation of pyrite by lead ions. This phenomenon is explained by different activation mechanisms. The pyrite activation by copper ions is considered to be an electrochemical process involving the formation of new Cu+-sulfide species. The greater concentration of Cu+ species in the solution and the greater proportion of sulfide on the pyrite surface at the more reducing grinding condition favor the copper activation process. In contrast, pyrite activation by lead ions is not dependent on the electrochemical potential and this parameter does not affect the concentration of lead species adsorbed onto the pyrite surface regardless of surface pre-oxidation. Thus, these conclusions provide a guide as to how to control pyrite activation through the manipulation of electrochemical potential during grinding. (C) 2011 Elsevier B.V. All rights reserved.