A low-pressure steady-state technique has been used to investigate the rates and mechanisms of the oxidation of isobutane over H-3[PMo12O40], CuH4[PMo12O40](2), Cu2H2[PMo12O40](2), CU2.5H[PMo12O40](2), and CU3[PMo12O40](2). Observed oxidation products over all catalysts are methacrolein, 3-methyl-2-oxetanone, acetic acid, carbon dioxide and water. The most selective catalyst for methacrolein formation at low temperatures (< 496 degrees C) is CU2.5H[PMo12O40](2), where both Cu(II) reduction and acid sites play a role. The least active catalyst at low temperatures is phosphomolybdic acid followed by CU3[PMo12O40](2). This activity is reversed at higher temperatures. The 3-methyl-2-oxetanone is a unique product and is likely to be the precursor to methacrylic acid. Acetic acid is also probably a precursor to complete oxidation. Catalyst deactivation or restructuring is significant only over H-3[PMo12O40]. Crown Copyright (C) 2007 Published by Elsevier B.V. All rights reserved.