Technical Abstract: The Hessian fly, Mayetiola destructor (Say), is present in all wheat producing regions of the United States and is the most important insect pest in the southeastern soft-winter-wheat region. Genotypes of the pest that can overcome formerly resistant wheat continue to appear and pose a threat to wheat production. There is a need to better understand the mechanisms by which resistant plants are able to prevail over larval attack. The goal of the present study was to determine if ultrastructural changes occur in the midguts of larvae feeding on resistant wheat compared to larvae feeding on susceptible wheat and larvae experiencing starvation while removed from the plant. Results revealed that within three hours of initiating feeding on resistant wheat midgut microvilli were disrupted and after six hours microvilli were absent. The disruptions in microvilli observed in larvae feeding on resistant wheat were similar to those reported for midgut microvilli of Drosophila melanogaster larvae fed a diet containing 1% wheat germ agglutinin. Results from the present ultrastructural study, coupled with previous gene expression studies, confirm the larval Hessian fly’s midgut is a major target of toxic plant compounds that play a pivotal role in resistance.