In Escherichia coli, at least 31 genes, which are involved in the roles related to the transport and assimilation of phosphate and phosphorus compounds, are induced by phosphate starvation. They constitute a single phosphate (pho) regulon, and are under the same physiological and genetic control (30, 36, 46). Proteins PhoB and PhoR, which are regulatory systems for the transcriptional regulation of the phogenes, belong to a large family of two-component regulatory systems that respond to a variety of environmental stimuli in bacteria (23, 24, 33, 39). PhoB is the transcriptional activator, which binds to the promoters of the pho genes (21, 22). PhoR is a transmembrane protein that modulates the activity of PhoB by promoting specific phosphorylation and dephosphorylation of PhoB in response to the phosphate signal in the medium (19, 21, 37, 50). The phosphorylation of PhoB protein occurs concurrently with the acquisition of the ability to activate transcription from the pho promoters (Fig. 1). In the absence of the PhoR functions, PhoB is phosphorylated independently of the phosphate levels by PhoM, a PhoR like protein (2, 3, 26), which was renamed CreC by Wanner (45). In this article, we describe our recent studies on the mechanism of the transcriptional regulation of the pho regulon.