Dirigent proteins regulate monolignol coupling to generate lignans (structural cell wall polymer) that are known to play a role in plant defense (as antioxidants and biocides) against pathogens and pests. Microarray expression profiling of wheat (Triticum aestivum) crown tissue showed the accumulation of dirigent-like protein-encoding gene transcripts in response to infestation by Hessian fly (Mayetiola destructor), a major dipteran pest. Here we report the cloning and temporal expression analysis of a Hessian fly-responsive dirigent-like gene (designated as HfrDir) in wheat. Quantitative real time transcriptional analysis of HfrDir during compatible (virulent larva, susceptible plant) and incompatible (avirulent larva, resistant plant) interactions revealed higher level of transcripts in the resistant wheat as compared to the susceptible or uninfested control plants. The potential roles of wheat dirigent gene in defense against Hessian fly are discussed.