Fragments of five rrp genes encoding response regulators (RRs) in Lactobacillus sakei were amplified by PCR using degenerate oligonucleotide primers. The five rrp genes were part of distinct loci that also comprised hpk genes encoding histidine protein kinases (HPKs). The putative RRs belonged to the OmpR-PhoB subclass of response regulators that consist of N-terminal receiver and C-terminal DNA-binding domains. The putative HPKs were members of the EnvZ-NarX family of orthodox histidine protein kinases which possess two transmembrane segments in a non-conserved N-terminal domain and a C-terminal cytoplasmic kinase domain. Insertional inactivation of the rrp genes indicated that the RRs are implicated in susceptibility to the glycopeptide antibiotic vancomycin, and to extreme pH, temperature and oxidative conditions.