Expression of Escherichia coli outer-membrane porin proteins (OmpF and OmpC) is regulated by the osmolarity of the medium. EnvZ and OmpR, which are positive regulatory factors for the transcriptional osmotic regulation of the ompF and ompC genes, belong to a group of two-component regulatory factors that respond to a variety of environmental stimuli in bacteria. EnvZ-OmpR phosphotransfer was revealed to be involved in signal transduction in response to an osmotic stimulus, and to play a crucial physiological role in the consequent osmotic activation of the porin genes. Based on the various lines of experimental evidence, a model is proposed for the molecular mechanism underlying the osmotic regulation through phosphorylation of the activator (OmpR) by the membrane-located kinase (Env2).