The reaction of methanol on oxidized Mo(110) surfaces is investigated using temperature-programmed reaction and a combination of high-resolution electron energy loss and infrared reflectance-absorbance spectroscopies. By varying conditions for preparation of surface oxide layers, we show that changes in reactivity in the presence of Mo=O species are in fact due to changes in the overall surface oxygen content : rather than to special reactivity at terminal sites, as was previously proposed. On the basis of these investigations, we propose that methanol reaction is promoted at open high-coordination sites. Infrared spectroscopy demonstrates that oxygen from this reaction is deposited in high-coordination sites only, even in the presence of Mo=O species, consistent with the reaction pathway for methanol on less highly oxidized Mo(110) surfaces.