In this study, we describe the first response regulator of Streptococcus suis serotype 2, designated RevS. RevS was cloned and the sequence was determined. No histidine kinase was found in the vicinity ofrevS, therefore RevS was considered to be an orphan response regulator. An isogenic knock-out mutant of RevS was shown to be attenuated in colonising the S. suis specific organs in a competitive assay in four piglets, indicating thatrevS plays a role in the pathogenesis of S. suis infections. We analysed the protein expression profiles of various fractions of the wild-type strain 10 and the mutant strain 10DeltaRevS. The expression of known virulence factors ofS. suis by wild-type and the mutant strain, was not different. However, one protein in the protoplast fraction, with unknown identity was shown to be repressed by revS in the exponential growth phase of the mutant.