Technical Abstract: We analyzed the accumulation of six phytohormones and phytohormone-related compounds in a wheat [Triticum aestivium (L.)] genotype ‘Molly’ following attacks by avirulent and virulent Hessian fly [Mayetiola destructor (Say)] larvae, respectively, and examined the expression of genes in the jasmonic acid (JA) pathway by Northern blot analysis. Attack by avirulent insects resulted in increased accumulation of salicylic acid (SA) by 11.3- and 8.2-fold, 12-oxo-phytodienoic acid (OPDA) by 36.4- and 18.7-fold, 18:3 fatty acid by 4.5- and 2.2-fold, and 18:1 fatty acid by 1.8- and1.9- fold at 24- and 72-hours post initial attack (hpia), respectively, but a 20% decrease in JA accumulation at 24-hpia. Attack by virulent insects did not affect the accumulation of SA, OPDA, 18:3 and 18:1 fatty acids, but resulted in a dramatic increase in auxin (AUX), with concentration from undetectable in uninfected plants to 381.7 ng/g fresh weight in 24-hpia and 71.0 ng/g fresh weight in 72-hpia in infested plants. Transcript levels of the genes encoding lipoxygenase 2 (LOX2), allene oxide synthase (AOS), and Arabidopsis storage protein 2 (AtVSP2) increased following avirulent larval attack, but decreased following virulent larval attack. Our results suggest that OPDA and SA may act together in wheat resistance to the Hessian fly, whereas AUX may play a role in the susceptibility of wheat plants. The increased OPDA accumulation resulting from avirulent larval attack was at least partially regulated through gene transcription.