Salmonella typhimurium is a facultative intracellular pathogen capable of surviving within host phagocytic cells. Salmonella strains carrying phoP mutations are avirulent, unable to survive in macrophages, and extremely sensitive to peptides having antimicrobial activity such as the host-derived defensins. We present here the DNA sequence of the phoP gene and show that the deduced amino acid sequence of phoP has extensive homology with the Escherichia coli transcriptional regulators PhoB and OmpR, which control the expression of loci in response to different environmental stimuli. The psiD locus, which is regulated by phosphate availability, was found to be under the control of the phoP gene product. Sequences homologous to phoP were found in several Gram-negative species and in the yeast Saccharomyces cerevisiae.