Streptococcal C5a peptidase (SCP), a recently discovered virulence factor of Streptococcus pyogenes, specifically cleaves the human serum chemotaxin C5a near its carboxyl terminus, destroying its ability to serve as a chemoattractant. We previously localized the SCP gene, scpA, to the 5.8-kb insert of the recombinant plasmid pTT1. Here we present the complete nucleotide sequence of scpA and its flanking regions. The gene initiates at a TTG codon and consists of 3501 base pairs, specifying a precursor protein of 128,252 daltons. Sequences resembling the promoter and ribosome-binding site of Gram-positive organisms are found upstream of scpA. The predicted amino acid sequence reveals the presence of a 31-residue signal peptide, putative cell wall spanning and membrane anchor domains. Regions of SCP show significant similarity to the sequences involved in the formation of the active site of the prokaryotic serine protease subtilisin. Results of Southern hybridization studies indicate that sequences highly similar to that of scpA are present in all serotypes of S. pyogenes tested.