For the selective oxidation of n-butane to maleic anhydride, (VO)[subscript]2P[subscript]2O[subscript]7 has been identified as the most active and selective V-P-O phase. However, the presence of various types of oxygen species present in this polyfunctional system has made it difficult to study its redox mechanism in terms of the different oxygen species present. To overcome this problem, we have employed isotopic reactive-site mapping (IR-SM) approach. A three stage solid state procedure was used to synthesize a (VO)[subscript]2P[subscript]2O[subscript]7 catalyst labeled with [superscript]18O. Characterization of this labeled catalyst by infrared and Raman spectroscopies, along with other complimentary techniques allowed to determine the location and the extent of the [superscript]18O labeling in the lattice oxygen sites. This evidence pointed to a highly site-specific [superscript]18O labeling. Anaerobic pulse micro-reactor studies using C[subscript]4 hydrocarbons (n-butane, 1-butene) as reactants were conducted with this labeled catalyst. [superscript]18O incorporation into the oxygenated products was determined by mass spectrometry. A comparison between the [superscript]18O content of products to those in various catalyst lattice sites allowed to associate specific surface layer reactive sites with the different mechanistic steps in the selective and nonselective pathways for n-butane conversion by (VO)[subscript]2P[subscript]2O[subscript]7 catalyst. These studies further revealed that n-butane is irreversibly chemisorbed and activated at the vanadyl dimer sites in a highly specific manner. Oxygen insertion at nearby V-O/[superscript] P-V sites leads to form a furan-like surface species, which undergoes additional oxygen addition at P-O-V sites forming maleic anhydride. More than one nonselective pathways were evident: either by the direct combustion of n-butane, involving its cracking at V = O sites; or by the consecutive oxidation of the reaction intermediates and maleic anhydride. Reactivity of a site was found to be dependent on the nature of the hydrocarbon feed. Thus, the initial interaction of n-butane was found to be fundamentally different as compared to that of 1-butene. Quantitative measurements showed that participation of the bulk oxygen is limited, and the redox mechanism is thus limited to a few near surface monolayers.