The reaction of methanol on TiO2(110)-supported vanadium oxide was studied using temperature-programmed desorption (TPD) and high-resolution electron energy loss spectroscopy (HREELS). TPD results show that methanol is oxidized to formaldehyde on monolayer and submonolayer vanadia films on TiO2(110), whereas both clean TiO2(110) and multilayer vanadia films supported on TiO2(110) are relatively inactive for this reaction. HREELS results demonstrate that methoxides are the primary surface intermediates in the oxidation of methanol to formaldehyde on the supported vanadium layers. The reactivity trends obtained for the model catalysts used in this study are similar to those observed for high surface area analogues. This suggests that vanadia films supported on single-crystal metal oxide substrates are excellent model systems for studying the relationships between the structure and reactivity of supported oxide catalysts.