Ammoxidation reactions involve the activation of ammonia and its subsequent oxidation in order to obtain the desired nitrile. In this paper the role of NH3 interaction with the activity and selectivity of VSbO4 catalysts is investigated. Experimental data reveal that the catalyst ability to adsorb ammonia is related with its catalytic behaviour. Moreover, ammonia adsorption drives the formation of the active VSbO4 rutile phase for metal oxide contents close to the monolayer. Periodic DFT calculations indicate that ammonia strongly adsorbs on Bronsted sites, while Lewis acid sites lead to a favourable dissociation to NH2 and NH. It is demonstrated that the adsorption of NH3 and NHx preferentially involves isolated vanadium sites. The isolated vanadium sites in the vicinity of antimony sites seem to provide a unique local environment for the initial steps of the ammoxidation reaction. (C) 2010 Elsevier B.V. All rights reserved.