Localized attack by a necrotizing pathogen induces systemic acquired resistance (SAR) to subsequent attack by a broad range of normally virulent pathogens. Salicylic acid accumulation is required for activation of local defenses, such as pathogenesis-related protein accumulation, at the initial site of attack, and for subsequent expression of SAR upon secondary, distant challenge. Although salicylic acid moves through the plant, it is apparently not an essential mobile signal. We screened Agrobacterium tumefaciens transfer DNA (tDNA) tagged lines of Arabidopsis thaliana for mutants specifically compromized in SAR. Here we show that Defective in induced resistance 1-1 (dir1-1) exhibits wild-type local resistance to avirulent and virulent Pseudomonas syringae, but that pathogenesis-related gene expression is abolished in uninoculated distant leaves and dir1-1 fails to develop SAR to virulent Pseudomonas or Peronospora parasitica. Petiole exudate experiments indicate that dir1-1 is defective in the production or transmission from the inoculated leaf of an essential mobile signal. DIR1 encodes a putative apoplastic lipid transfer protein and we propose that DIR1 interacts with a lipid-derived molecule to promote long distance signalling.