A high molecular weight polyacrylamide (PAM) was tested as a potential selective depressant in the differential flotation separation of galena and chalcopyrite using potassium ethyl xanthate (KEX) as a collector. In single mineral flotation, PAM depressed chalcopyrite while galena was floatable. Adsorption mechanism study indicated that PAM could adsorb on galena through hydrogen bonding, and on chalcopyrite through hydrogen bonding as well as ammonium-copper complexation. KEX could only break up the galena-PAM bonding. Therefore the combined use of PAM and KEX rendered the flotation of the two minerals selective. In the flotation of mixtures of the two minerals, galena and chalcopyrite could be separated by PAM and KEX only after EDTA treatment of the mineral mixtures. Time of flight secondary ion mass spectrometric (ToF-SIMS) measurements indicated that when galena and chalcopyrite were present together in the suspension, PAM adsorbed on both galena and chalcopyrite. However, after prior treatment of the mineral mixtures by EDTA, PAM was found to mainly adsorb on chalcopyrite. (C) 2014 Elsevier B.V. All rights reserved.