The enhanced disease resistance 1 (edr1) mutation of Arabidopsis confers resistance to powdery mildew disease caused by the fungus Erysiphe cichoracearum. Resistance mediated by the edr1 mutation is correlated with induction of several defense responses, including host cell death. Double mutant analysis revealed that all edr1-associated phenotypes are suppressed by mutations that block salicylic acid (SA) perception (nim1) or reduce SA production (pad4 and eds1). The NahG transgene, which lowers endogenous SA levels, also suppressed edr1. In contrast, the ein2 mutation did not suppress edr1-mediated resistance and associated phenotypes, indicating that ethylene and jasmonic acid-induced responses are not required for edr1 resistance. The EDR1 gene was isolated by positional cloning and was found to encode a putative MAP kinase kinase kinase similar to CTR1, a negative regulator of ethylene responses in Arabidopsis. Taken together, these data suggest that EDR1 functions at the top of a MAP kinase cascade that negatively regulates SA-inducible defense responses. Putative orthologs of EDR1 are present in monocots such as rice and barley, indicating that EDR1 may regulate defense responses in a wide range of crop species. P lants defend themselves against infectious diseases by using both preformed and induced defenses. The latter comprise a complex suite of physiological changes, including a form of programmed cell death called the hypersensitive resistance response (HR) (1). In an effort to identify plant genes that regulate defense responses, we screened for Arabidopsis mutants that displayed enhanced resistance to normally virulent pathogens. The edr1 mutant was identified in a screen for mutants that had become resistant to the bacterium Pseudomonas syringae and was subsequently shown to be resistant to Erysiphe cichoracearum (powdery mildew) (2). Significantly, edr1 mutant plants do not display constitutive expression of the defense gene PR-1, indicating that resistance is not caused by constitutive activation of systemic acquired resistance-associated defenses (3).Although known defense responses are not constitutively expressed in edr1 plants, several defense responses are induced by E. cichoracearum more rapidly in edr1 plants than in wild-type Arabidopsis variety Col-0 (2). These include deposition of autofluorescent compounds and callose [a -(133) glucan] in mesophyll cell walls, accumulation of PR-1 mRNA, and mesophyll cell death. In wild-type Col-0 plants infected with E. cichoracearum, these defenses are induced more slowly, and very little cell death is observed (2, 4). Because the edr1 mutation is recessive, the EDR1 gene appears to function as a negative regulator. Because these defenses are not expressed in edr1 plants in the absence of pathogens, however, there must be pathogen-associated signals required to induce these defenses. In the absence of EDR1 function, even presumably weak signals from virulent Erysiphe strains are sufficient to induce strong responses.Because the edr1 mutant appears p...