As part of an ongoing study in our laboratory to elucidate the reactivities of the group V metal oxide clusters, reactions between vanadium and niobium oxide cations and methanol were conducted using a guided ion beam mass spectrometer coupled to a laser vaporization source. Size-specific cluster reactions were identified, with some indicated products being the same as those formed in methanol reactions over condensed phase niobia and vanadia catalysts, namely, H2CO and C2H6O. The effects of the properties of the clusters, among them size, stoichiometry, oxidation state, and composition on their reactivity toward methanol, are discussed.