Salicylic acid (SA)-dependent signaling controls activation of a set of plant defense mechanisms that are important for resistance to a variety of microbial pathogens. Many Arabidopsis mutants that display altered SA-dependent signaling have been isolated. We used double mutant analysis to determine the relative positions of the pad4, cpr1, cpr5, cpr6, dnd1 and dnd2 mutations in the signal transduction network leading to SA-dependent activation of defense gene expression and disease resistance. The pad4 mutation causes failure of SA accumulation in response to infection by certain pathogens, while the other mutations cause constitutively high levels of SA, defense gene expression and resistance. The cpr1 pad4, cpr5 pad4, cpr6 pad4, dnd1 pad4 and dnd2 pad4 double mutants were constructed and assayed for stature, presence of spontaneous lesions, resistance to Pseudomonas syringae and Peronospora parasitica, SA levels, expression of PAD4, PR-1 and PDF1.2, and accumulation of camalexin. We found that the effects of the cpr1 and cpr6 mutations on SA-dependent gene expression are completely dependent on PAD4 function. In contrast, SA accumulation in the lesion-mimic mutant cpr5 is partially PAD4-independent, while in dnd1 and dnd2 mutants it is completely PAD4-independent. A model describing a possible arrangement of activities in the signal transduction network is presented.