Technical Abstract: Understanding the molecular basis of coevolutionary relationship between resistance genes in plants and the avirulence genes in the pathogen should benefit the development of methods to control plant diseases. Rice blast disease is one of the most damaging diseases worldwide. Rice blast disease has been under intensive studies over decades. Presently, the rice blast system is one of the best models to study the host-pathogen interactions. The Pi-ta gene in rice effectively prevents infection by races of Magnaporthe oryzae that contain the corresponding AVR gene, AVR-Pita. Pi-ta is a putative cytoplasmic protein with a centrally located nucleotide binding sites (NBS) and a leucine rich domain (LRD) at the carboxyl terminus. The Pi-ta gene has been deployed effectively in preventing rice blast in the southern US since 1990. AVR-Pita encodes a predicted metalloprotease. Its processed form, AVRPita 176, was shown to directly bind with the Pi-ta protein in triggering effective defense responses. Variants of AVR-Pita were identified in many contemporary M. oryzae races and in isolates collected during the last 30 years in the US. Sequence analysis of these AVR-Pita variants revealed that the AVR-Pita protein might be under diversified selection. Most recently, sequence analysis of the Pi-ta variants in six Oryza species (O. sativa, O. glaberrima, O. officialis, O. rufipogon, O. barthii and O. nivara) revealed that FNP918, a unique functional nucleotide polymorphism, is present among all these Oryzae species, and Pi-ta may be under balanced selection. We suggest that Pi-ta co-evolves with AVR-Pita, and that rice engages trench warfare with M. oryzae. Resistance genes thus can be identified from adapted rice cultivars worldwide. This knowledge is an important for identifying new resistance resources to prevent plant disease.