Density functional theory and the calculations of oxygen nucleophilicity have been applied to an analysis of the oxidative dehydrogenation (ODH) of propane on the (010) surface of V2O5. These calculations show that the energetically preferred initial step is the dissociative adsorption of propane to form i-propoxide and hydroxyl species. Two V=O groups [O(1)] bonded by a V-O-V bridge are required. One of the vanadyl groups attacks the beta -C atom of propane and is converted to a V-OCH2(CH3)(2) species, whereas the ether vanadyl group is converted into a V-OH group. The activation barrier for this process is 9.4 kcal/mol. Dissociative adsorption to form an n-propoxide can also occur, but the activation barrier for this process is 14.5 kcal/mol. Propene and water are formed via a concerted process in which an H atom of one of the methyl groups of i-propoxide reacts with an O(3)H group. Exploration of alternative pathways for this step reveals that neither O(1, 2, 3), O(1)H, nor O(2)H are sufficiently reactive. These findings are in good qualitative agreement with experimental observations concerning the mechanism and kinetics of propane ODH.