The behaviour of Cu-Fe and Ag-Fe powder blends plastically deformed in a high energy ball mill has been studied by transmission electron microscopy (TEM). Both systems do not show any intermediate phase or extended solid solution in the equilibrium phase diagram owing to their positive enthalpy of mixing. While Cu and Fe can be mixed in the liquid state, the enthalpy of mixing is so large in the Ag-Fe binary system that only a very limited solubility is observed even in the liquid state. Previous reported data show that upon high energy ball milling the former system forms a relatively homogeneous solid solution, while Ag and Fe do not show any appreciable solubility even after prolonged processing. The microstructural characterization of both systems, which show a different microstructure at the end of the milling process, and the comparison of their microstructural evolution during ball milling, allow to advance an hypothesis concerning the thermodynamic driving force giving rise to mechanical alloying in systems with a positive heat of mixing.