Arabidopsis nonexpresser of pathogenesis-related (PR) genes (NPR1) is the sole positive regulator that has been shown to be essential for the induction of systemic acquired resistance. In npr1 mutant plants, salicylic acid (SA)-mediated PR gene expression and pathogen resistance are abolished completely. NPR1 has been shown to interact with three closely related TGA transcription factors-TGA2, TGA5, and TGA6-in yeast two-hybrid assays. To elucidate the biological functions of these three TGA transcription factors, we analyzed single and combined deletion knockout mutants of TGA2, TGA5, and TGA6 for SA-induced PR gene expression and pathogen resistance. Induction of PR gene expression and pathogen resistance by the SA analog 2,6-dichloroisonicotinic acid (INA) was blocked in tga6-1 tga2-1 tga5-1 but not in tga6-1 or tga2-1 tga5-1 plants. Loss of INA-induced resistance to Peronospora parasitica Noco2 cosegregated with the tga6-1 mutation in progeny of multiple lines that were heterozygous for tga6-1 and homozygous for tga2-1 tga5-1 and could be complemented by genomic clones of wild-type TGA2 or TGA5, indicating that TGA2, TGA5, and TGA6 encode redundant and essential functions in the positive regulation of systemic acquired resistance. In addition, tga6-1 tga2-1 tga5-1 plants had reduced tolerance to high levels of SA and accumulated higher basal levels of PR-1 under noninducing conditions, suggesting that these TGA factors also are important for SA tolerance and the negative regulation of the basal expression of PR-1.