ENHANCED DISEASE RESISTANCE 1 (EDR1) is a negative regulator of powdery mildew resistance, cell death and ethylene-induced senescence. To identify components involved in EDR1 signaling, we performed a forward genetic screen for edr1 suppressors. In this screen, we identified the hpr1-4 mutation, which partially suppresses edr1-mediated resistance to the powdery mildew pathogen Golovinomyces cichoracearum and mildew-induced cell death. However, the hpr1-4 mutation enhanced the ethylene-induced senescence phenotype of edr1. The hpr1-4 single mutant displayed enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Arabidopsis HPR1 encodes a homolog of human HPR1, a component of the conserved THO/transcription export (THO/TREX) complex that is required for mRNA export in yeast and humans. HPR1 is expressed in various organs and throughout all developmental stages. HPR1 localizes to the nucleus, and, significantly, mRNA export is compromised in the hpr1-4 mutant. Taken together, these data demonstrate that HPR1 plays an important role in disease resistance in plants, and that the THO/TREX complex is functionally conserved among plants, yeast and humans. Our data indicate a general link between mRNA export, defense responses and ethylene signaling in plants.