Staphylococcus aureus is a leading cause of hospital- and community-associated infections. The organisms ability to cause disease can, in part, be attributable to its ability to adapt to otherwise deleterious host-associated stresses. Like other bacterial species, the modulation of mRNA turnover appears to play an important role in S. aureus adaptation to certain environmental stresses. In the current study Affymetrix GeneChips were used to examine the S. aureus responses to acid and alkaline shock-inducing conditions and to assess whether stress dependent changes in mRNA turnover are likely to facilitate the organisms ability to tolerate extreme pH challenge. Results indicate that S. aureus adapts to pH shock by eliciting responses expected of organisms coping with pH alteration, including neutralizing cellular internal pH, DNA repair, amino acid biosynthesis and virulence factor expression. Further, it was found that the cellular response to alkaline conditions elicits a transcriptional profile that is similar to that of stringent response induced cells. Consistent with that observation, we show that the activator of the stringent response, (p)ppGpp, levels are profoundly elevated during alkaline shock conditions. We also show that the mRNA turnover properties of acid or alkaline shocked cells significantly differ from that of cells grown at neutral pH. A comparison of the mRNA degradation properties of transcripts whose titers either increased or decreased in response to sudden pH change revealed that alterations in mRNA degradation may, in part, account for the changes in the mRNA levels of factors predicted to mediate pH tolerance. Finally, a set of small stable RNA molecules were induced in response to acid or alkaline shock conditions. As in other organisms, these molecules may mediate mRNA stability and adaptation to otherwise deleterious growth conditions.