Marteyn et al. have investigated the role of oxygen and the regulator FNR in infection by the intracellular enteric pathogen Shigella flexneri. FNR is active under anaerobic conditions like those present in the lumen of the distal intestine. FNR causes elongation of a secretion apparatus required for bacterial entry into cells and represses secretion of proteins that trigger entry. Higher oxygen levels present at the intestinal cell surface are sufficient to inactivate FNR, thereby derepressing secretion. Thus, bacteria are 'primed' in the anaerobic environment of the lumen, and entry is triggered by the aerobic conditions at the intestinal cell surface. FNR is conserved among many enteric pathogens, suggesting that regulation of virulence in response to oxygen may be widely conserved.