In plants, systemic acquired resistance (SAR) is established as a result of NPR1-regulated expression of pathogenesis-related (PR) genes. Using gene expression profiling in Arabidopsis, we found that in addition to controlling the expression of PR genes, NPR1 also directly controls the expression of the protein secretory pathway genes. Up-regulation of these genes is essential for SAR, because mutations in some of them diminished the secretion of PR proteins (for example, PR1), resulting in reduced resistance. We provide evidence that NPR1 coordinately regulates these secretion-related genes through a previously undescribed cis-element. Activation of this cis-element is controlled by a transcription factor that is translocated into the nucleus upon SAR induction.