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Bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is the most destructive bacterial disease of rice. The cloned rice gene Xa21 confers resistance to a broad spectrum of Xoo races. To identify genes involved in Xa21‐mediated immunity, a whole‐genome oligonucleotide microarray of rice was used to profile the expression of rice genes between incompatible interactions and mock treatments at 0, 4, 8, 24, 72 and 120 h post inoculation (hpi) or between incompatible and compatible interactions at 4 hpi, respectively. A total of 441 differentially expressed genes, designated as XDGs (Xa21 mediated differentially expressed genes), were identified. Based on their functional annotations, the XDGs were assigned to 14 categories, including defense‐related, signaling, transcriptional regulators. Most of the defense‐related genes belonged to the pathogenesis‐related gene family, which was induced dramatically at 72 and 120 hpi. Interestingly, most signaling and transcriptional regulator genes were downregulated at 4 and 8 hpi, suggesting that negative regulation of cellular signaling may play a role in the Xa21‐mediated defense response. Comparison of expression profiles between Xa21‐ and other R gene‐mediated defense systems revealed interesting common responses. Representative XDGs with supporting evidences were also discussed. [ABSTRACT FROM AUTHOR]