Arabidopsis MAP Kinase 4 (MPK4) negatively regulates systemic acquired resistance (SAR). Transposon inactivation of MPK4 produced the mpk4 mutant, which exhibited constitutive SAR, including elevated salicylic acid (SA) levels, increased resistance to pathogens, and constitutive expression of pathogenesis-related (PR) genes. MPK4 kinase activity is required to repress SAR, as an inactive MPK4 form failed to complement the mpk4 mutant. Analysis of mpk4 expressing the SA hydroxylase NahG and of mpk4/npr1 double mutants indicated that SAR in mpk4 is dependent on elevated SA levels but independent of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression. The mpk4 mutant exhibits constitutive defense responses without spontaneous necrotic lesions, including elevated SA levels and resistance to oomycete and bacterial pathogens. RNA blot and cDNA microarray hybridizations showed that the mutant constitutively expresses PR genes normally induced by SA and fails to induce PDF1.2 and THI2.1 mRNA in response to JA. Molecular cloning, revertant analysis, and complementation studies demonstrated that the mpk4 phenotype is caused by loss of MPK4 activity. These data suggest a role of MPK4 in regulating plant defenses against pathogens. The mpk4 mutant does not exhibit necrotic lesions and does not fall into the common class of lesion-mimic mutants. The lack of spontaneous cell death in mpk4 is critical, as disruption of normal cell function might be expected to turn on PCD pathways. Additionally, if the mpk4 phenotype were a pleiotropic effect of an unbalanced biochemical state, a general activation of defenses, including SA- and JA-dependent pathways, might be expected. However, in mpk4, these two major defense pathways are oppositely affected, since SA-dependent defenses are constitutively expressed, while induction of JA-dependent defense genes is blocked. Microarray hybridization showed no other obvious differences than in defense-related transcripts, suggesting that SAR expression is the only deviation from homeostasis in mpk4. Furthermore, mpk4 responded normally to a range of abiotic stresses and phytohormones, and MPK4 is therefore not involved in responses to these stimuli. MPK4 is constitutively active under normal conditions and its activity is required to repress SAR, since the inactive MPK4 mutant failed to complement the dwarf and PR1 expression phenotypes of mpk4. This argues that inappropriate cross-talk between MAPK isoforms in the mpk4 mutant is not the cause of constitutive SAR expression. Thus, SAR is negatively regulated by MPK4 kinase activity. NahG abolishes PRArabidopsis MAP Kinase 4 (MPK4) negatively regulates systemic acquired resistance (SAR). Transposon inactivation of MPK4 produced the mpk4 mutant, which exhibited constitutive SAR, including elevated salicylic acid (SA) levels, increased resistance to pathogens, and constitutive expression of pathogenesis-related (PR) genes. MPK4 kinase activity is required to repress SAR, as an inactive MPK4 form failed to complement the mpk4 mutant. Analysis of mpk4 expressing the SA hydroxylase NahG and of mpk4/npr1 double mutants indicated that SAR in mpk4 is dependent on elevated SA levels but independent of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression. The mpk4 mutant exhibits constitutive defense responses without spontaneous necrotic lesions, including elevated SA levels and resistance to oomycete and bacterial pathogens. RNA blot and cDNA microarray hybridizations showed that the mutant constitutively expresses PR genes normally induced by SA and fails to induce PDF1.2 and THI2.1 mRNA in response to JA. Molecular cloning, revertant analysis, and complementation studies demonstrated that the mpk4 phenotype is caused by loss of MPK4 activity. These data suggest a role of MPK4 in regulating plant defenses against pathogens. The mpk4 mutant does not exhibit necrotic lesions and does not fall into the common class of lesion-mimic mutants. The lack of spontaneous cell death in mpk4 is critical, as disruption of normal cell function might be expected to turn on PCD pathways. Additionally, if the mpk4 phenotype were a pleiotropic effect of an unbalanced biochemical state, a general activation of defenses, including SA- and JA-dependent pathways, might be expected. However, in mpk4, these two major defense pathways are oppositely affected, since SA-dependent defenses are constitutively expressed, while induction of JA-dependent defense genes is blocked. Microarray hybridization showed no other obvious differences than in defense-related transcripts, suggesting that SAR expression is the only deviation from homeostasis in mpk4. Furthermore, mpk4 responded normally to a range of abiotic stresses and phytohormones, and MPK4 is therefore not involved in responses to these stimuli. MPK4 is constitutively active under normal conditions and its activity is required to repress SAR, since the inactive MPK4 mutant failed to complement the dwarf and PR1 expression phenotypes of mpk4. This argues that inappropriate cross-talk between MAPK isoforms in the mpk4 mutant is not the cause of constitutive SAR expression. Thus, SAR is negatively regulated by MPK4 kinase activity. NahG abolishes PR