In situ environmental high-resolution electron microscopy (in situ EHREM) under different gaseous environments and ex situ HREM have been used to directly probe commercially important vanadyl pyrophosphate ((VO)(2)P2O7) catalysts used in the oxidation of n-butane to maleic anhydride. These fundamental studies of catalyst-adsorbate interactions have shown that novel microstructural changes occur in vanadyl pyrophosphate catalysts when the catalyst is reduced,partially oxidized, or exposed to N-2 and steam environments for extended periods of 100-300 h for the first time. The microstructural changes of vanadyl pyrophosphates are related to the development of extended misfit glide shear plane defects accommodating nonstoichiometry. The complex characteristics of long-term. effects of water vapor and the effect of cation promoters of iron and antimony in vanadyl pyrophosphates are explored to improve our understanding of their effects on the catalysts toward n-butane oxidation, Correlations of microstructural changes with reaction chemistry suggest that the changes are associated with catalyst reactivity and lattice oxygen diffusion sates.