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Like other bacterial species, Mycobacterium tuberculosis has multiple sigma (σ) factors encoded in its genome. In previously published work, we and others have shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and, in some cases, cause attenuated virulence phenotypes. In this paper, we characterize a M. tuberculosis mutant lacking the ECF σ factor σ^H. This mutant was more sensitive than the wild type to heat shock and to various oxidative stresses, but did not show de‐creased ability to grow inside macrophages. Using quantitative reverse transcription‐PCR and microarray technology, we have started to define the σ^H regulon and its involvement in the global regulation of the response to heat shock and the thiol‐specific oxidizing agent diamide. We identified 48 genes whose expression increased after exposure of M. tuberculosis …