Both solid-solid and gas-solid reactions have been traced during high-energy milling of Se and PbO powders under vial (P,T) conditions in order to synthesize the PbSe phase. Chemical and thermodynamic arguments are postulated to discern the high-energy milling mechanism to transform PbO-Se micropowders onto PbSe-nanocrystals. A set of reactions were evaluated at around room temperature. Therefore an experimental campaign was designed to test the nature of reactions in the PbO-Se system during high-energy milling. (C) 2011 Elsevier Ltd. All rights reserved.