One of the major signalling pathways responsible for intercompartmental communication between the cell envelope and cytoplasm in Escherichia coli is mediated by the alternative sigma factor, σE. σE has been studied primarily for its role in response to the misfolding of outer membrane porins. This response is essentially reactionary; cells are stressed, porin folding is disrupted, and the response is activated. σE can also be activated following starvation for a variety of nutrients by the alarmone ppGpp. This response is proactive, as σE is activated in the absence of any obvious damage to the cell envelope sensed by the stress signalling pathway. Here we examine the mechanism of regulation of σE by ppGpp. ppGpp has been proposed to activate at least two alternative sigma factors, σN and σS, indirectly by altering the competition for core RNA polymerase between the alternative sigma factors and the housekeeping sigma factor, σ70. In vivo experiments with σE are consistent with this model. However, ppGpp and its cofactor DksA can also activate transcription by EσEin vitro, suggesting that the effects of ppGpp on σE activity are both direct and indirect.