Bordetella pertussis, the causative agent of whooping cough, coordinately regulates the expression of its virulence factors in response to certain environmental stimuli. This coordinate regulation is accomplished by the bvg locus encoding the BvgS and the BvgA proteins, which are members of the two-component family of bacterial signal transducing proteins. The sensor protein BvgS shows an "unorthodox" domain structure, combining the characteristic communication modules both of the two component sensors and response regulators, each of which is indispensable for BvgS function. Although under global control of the BvgAS system, two subsets of virulence factors exemplified by the adhesin FHA and the toxins PTX and CYA exhibit, respectively, a differential mode of expression. This is reflected in a differential kinetics of transcriptional activation in vivo, and the different ability of the various virulence promoters to be expressed in the heterologous organism Escherichia coli. Evidence is accumulating that this differential regulation may be due to different affinities of the virulence promoters for the phosphorylated form of BvgA.