The Pho regulon of Bacillus subtilis is controlled by three two-component signal-transduction systems: PhoP/PhoR, ResD/ResE, and the phosphorelay leading to the phosphorylation of SpoOA. Two of these systems act as positive regulators, while the third is involved in negative regulation of the Pho regulon. Under phosphate-starvation-induction conditions, the response regulator (RR) PhoP, and the histidine protein kinase (HK) PhoR, are involved in the induction of Pho-regulon genes including the phoPR operon and genes encoding the major vegetative alkaline phosphatases, phoA and phoB. ResD (the RR) and ResE (the HK) are positive regulators of both aerobic and anaerobic respiration in B. subtilis. Current data suggest that they are also positive regulators of the Pho regulon, as is the transition-state regulatory protein AbrB. Data presented reveal that ResDE and AbrB are involved in activation of the Pho regulon through separate regulatory pathways. SpoOA approximately P (RR) exerts a negative effect on the Pho regulon through its repression of AbrB, and possibly through repression of ResDE. Both pathways converge to regulate transcription of the phoPR operon.