A Staphylococcus aureus gene originally identified by signature-tagged mutagenesis as being required for virulence was cloned, sequenced and named svrA. Hydropathy profiles revealed that SvrA is likely to be membrane associated, having two regions with six membrane-spanning domains, the regions separated by an extended hydrophilic loop. When compared with the wild-type strain, an svrA mutant expressed greatly reduced amounts of alpha-, beta- and delta-toxins and an increased amount of protein A. Toxin production by the mutant strain was restored to wild-type levels when complemented with a plasmid expressing the svrA gene. Northern hybridization with probes specific for hla (encoding alpha-toxin) and spa (encoding protein A) showed that the svrA mutant strain was affected in the transcription of these genes. svrA mRNA was present in wild-type and agr strains, but agr mRNA and RNAIII were absent in the svrA mutant strain. Virulence studies suggested that the attenuation of the svrA mutant was probably due to its direct or indirect effect on the agr regulon. These results indicate that svrA is required for the expression of agr and RNAIII transcripts and is therefore a new component of the agr regulatory network controlling virulence gene expression in S. aureus.