The oxidation of fatty acids, which is responsible for changes in lipid composition, were investigated in a comparative study using the Russian wheat aphid (RWA) (Diuraphis noxia), infested and un-infested resistant (Tugela DN) and close isogenic-susceptible (Tugela) wheat cultivars. LOX, which catalyzes the first step of the lipoxygenase pathway, was selectively induced in the infested resistant wheat. A pathogen-induced oxygenase protein was also found to be induced during the wheat-RWA interaction. The involvement of oxylipins in the RWA resistance response was confirmed by inhibition studies using indomethacin, which is known to inhibit prostanoid biosynthesis in mammalian tissue. Downstream defense reactions, e.g. LOX and POD activities, were inhibited upon indomethacin treatment. These results emphasize the importance of fatty acid oxidation as an essential process for the establishment of a successful defense response in wheat to the RWA.