The σ^S subunit of Escherichia coli RNA polymerase regulates the expression of stationary phase and stress response genes. σ^S is highly unstable in exponentially growing cells, whereas its stability increases dramatically upon starvation or under certain stress conditions. The degradation of σ^S is controlled by the phosphorylatable adaptor protein RssB and the ClpXP protease. RssB specifically directs σ^S to ClpXP. An unanswered question is how RssB-mediated degradation of σ^S is blocked by conditions such as glucose or phosphate starvation. We report here the identification and characterization of a new regulator of σ^S stability, IraP (inhibitor of RssB activity during phosphate starvation), that stabilizes σ^S both in vivo and in vitro. Deletion of iraP interferes with σ^S stabilization during phosphate starvation, but not during carbon starvation, and has a partial effect in stationary phase and nitrogen starvation. IraP interferes with RssB-dependent degradation of σ^S through a direct protein–protein interaction with RssB. A point mutant of IraP was isolated and found to be defective both for inhibition of σ^S degradation and interaction with RssB. Our results reveal a novel mechanism of regulation of σ^S stability through the regulation of RssB activity and identify IraP as a member of a new class of regulators, the anti-adaptor proteins.