BACKGROUND: Gamma-proteobacteria, such as Escherichia coli, can use a variety of respiratory substrates employing numerous aerobic and anaerobic respiratory systems controlled by multiple transcription regulators. Thus, in E. coli, global control of respiration is mediated by four transcription factors, Fnr, ArcA, NarL and NarP. However, in other Gamma-proteobacteria the composition of global respiration regulators may be different. RESULTS: In this study we applied a comparative genomic approach to the analysis of three global regulatory systems, Fnr, ArcA and NarP. These systems were studied in available genomes containing these three regulators, but lacking NarL. So, we considered several representatives of Pasteurellaceae, Vibrionaceae and Yersinia spp. As a result, we identified new regulon members, functioning in respiration, central metabolism (glycolysis, gluconeogenesis, pentose phosphate pathway, citrate cicle, metabolism of pyruvate and lactate), metabolism of carbohydrates and fatty acids, transcriptional regulation and transport, in particular: the ATP synthase operon atpIBEFHAGCD, Na+-exporting NADH dehydrogenase operon nqrABCDEF, the D-amino acids dehydrogenase operon dadAX. Using an extension of the comparative technique, we demonstrated taxon-specific changes in regulatory interactions and predicted taxon-specific regulatory cascades. CONCLUSION: A comparative genomic technique was applied to the analysis of global regulation of respiration in ten gamma-proteobacterial genomes. Three structurally different but functionally related regulatory systems were described. A correlation between the regulon size and the position of a transcription factor in regulatory cascades was observed: regulators with larger regulons tend to occupy top positions in the cascades. On the other hand, there is no obvious link to differences in the species' lifestyles and metabolic capabilities.