An Arabidopsis PR1::luciferase (LUC) transgenic line was transformed with activation T-DNA tags and the resulting population screened for dominant gain-of-function mutants exhibiting constitutive LUC activity. LUC imaging identified activated disease resistance 2 (adr2), which exhibited slowly spreading lesions in the absence of pathogen challenge. Molecular, genetic and histochemical analysis was employed to characterize this mutant in detail. adr2 plants constitutively expressed defence-related and antioxidant genes. Moreover, this line accrued increased quantities of salicylic acid (SA) and exhibited heightened mitogen-activated protein kinase activity. adr2 plants exhibited increased resistance against numerous biotrophic but not necrotrophic pathogens. The adr2 phenotype resulted from the overexpression of a Toll interleukin receptor (TIR) nucleotide binding site (NBS) leucine rich repeat (LRR) gene (At1g56510). Constitutive PR1 expression was completely abolished in adr2 nahG, adr2 npr1 and adr2 eds1 double mutants. Furthermore, heightened resistance against Hyaloperonospora arabidopsis Noco2 was compromised in adr2 nahG and adr2 eds1 double mutants but not in adr2 npr1, adr2 coi1 or adr2 etr1 plants. These data imply that adr2-mediated resistance operates through an Enhanced Disease Susceptibility (EDS) and SA-dependent defence signalling network which functions independently from COI1 or ETR1.