Technical Abstract: Pi-ta-mediated resistance in rice controls strains of the rice blast fungus that express avirulent alleles of AVR-Pita in a gene-for-gene manner. Map-based cloning of AVR-Pita identified a gene predicted to encode a neutral zinc metalloprotease. We also cloned Pi-ta, a centromere-linked resistance gene on rice chromosome 12, using a map-based cloning strategy. It encodes a predicted 928-amino acid cytoplasmic receptor with a centrally localized nucleotide-binding site. Pi-ta is a single-copy gene and it shows constitutive low-level expression in both resistant and susceptible lines of rice. Susceptible rice lines contain pi-ta alleles encoding proteins that share in common one amino acid difference relative to the Pi-ta resistance protein, serine instead of alanine at position 918. Direct interaction of the Pi-ta and AVR-Pita proteins was demonstrated using the yeast two-hybrid system and in vitro binding assays. Our current hypothesis is that the Pi-ta protein is an intracellular receptor that binds to the mature AVR-Pita protease inside the host cell, initiating Pi-ta-mediated defense responses. Understanding how pathogen recognition occurs provides the opportunity to manipulate recognition specificity. Population analysis of AVR gene structure and dynamics will aid in the deployment of resistance genes. The relationship between the Pi-ta and Pi-ta² genes is discussed.