Forty-eight resistance (R) genes conferring resistance to various types of pests have been cloned from 12 plant species. Irrespective of the host or the pest type, most R genes share a strong protein sequence similarity especially for domains and motifs. The objective of this study was to identify expressed R genes of wheat, the fraction of which is expected to be very low in the genome. Using modified RNA fingerprinting and data mining approaches we identified 220 expressed R-gene candidates. Of these, 125 sequences structurally resembled known R genes. In addition to 25-87% protein sequence similarity with the known R genes, the sequence, order, and distribution of the domains and motifs were also the same. Among the remaining 95, 17 were probable R-related, 21 were a new class of nucleotide-binding kinases, 21 were probable kinases, and 36 were p-loop-containing unknown sequences. About 76% were rare including 73 novel sequences. Three new R-gene specific motifs were also identified. Physical mapping of the 164 best R-gene candidates on 339 deletion lines localized 121 mappable R-gene candidates to 26 small chromosomal regions encompassing about 16% of the genome. About 90 of the 110 phenotypically characterized wheat R genes corresponding to 18 different pests also mapped in these regions.