The differentially virulent race T1 of common bunt (Tilletia tritici) was used to inoculate the wheat lines Neepawa (compatible) and its sib BW553 (incompatible) that are nearly isogenic for the Bt-10 resistance gene. Inoculated crown tissues were used to construct a suppression subtractive hybridization (SSH) cDNA library. Of the 1920 clones arrayed from the SSH cDNA library, approximately 10% were differentially regulated. A total of 168 differentially up-regulated and 25 down-regulated genes were identified and sequenced; 71% sequences had significant homology to genes of known function, of which 59% appeared to have roles in cellular metabolism and development, 24% in abiotic/biotic stress responses, 3% involved in transcription and signal transduction responses. Two putative resistance genes and a transcription factor were identified among the up regulated sequences. The expression of several candidate genes including a lipase, two non-specific lipid transfer proteins (ns-LTPs), and several wheat pathogenesis-related (PR)-proteins, was evaluated following 4 to 32 days post-inoculation in compatible and incompatible interactions. Results confirmed the higher overall expression of these genes in resistant BW553 compared to susceptible Neepawa, and the differential up-regulation of wheat lipase, chitinase and PR-1 proteins in the expression of the incompatible interaction.