Previously we described a long-polymerase chain reaction (PCR) method to amplify a 4-7 kb target containing most of the components of the vir regulon (mga, emm-like genes and scpA) in a number of group A streptococcus (GAS) isolates. In contrast to GAS, strains of human group G streptococcus (GGS) gave approximately 1.6 or 1.8 kb products. Sequence analysis of the amplified products issued from GGS templates revealed a mosaic consisting of upstream sequence from mga (the gene for positive regulator of vir regulon), an unidentified open reading frame, a short segment of emm (the gene for M protein, an antiphagocytic molecule) and an upstream sequence of scp (C5a-peptidase gene). A full length scpG is present immediately downstream from the mosaic segment in the human GGS genome. The GGS PCR fragment did not code for mga or full length emm. All human GGS isolates are known to code for emm but the gene is separated from scpG by at least 10 kb. Our data, obtained using long-PCR and unrelated strains of GGS, confirm this. We could not detect a homologue of mga in human GGS by hybridization analysis. The mosaic sequence suggests that enbloc transfer of the vir regulon from GAS to a GGS progenitor may have occurred, following which deletion and rearrangement events may have taken place. Partial nucleotide sequences of emm corresponding to the variable domain of M proteins from three local GGS isolates were determined. One sequence (emmGGS6) is 99% identical to emm from a geographically separated isolate of GGS recently described.3 emmGGS6 also has significant homology with emm from a GAS strain (STDONALD) isolated from the same geographical area as was GGS6. The two emm sequences (emmGGS6 and emmSTDONALD) revealed frameshift-compensatory frameshift mutations relative to each other, contributing to lower amino acid homology between the two predicted M proteins. Since emmSTDONALD has no known relatives within the 80 or so emm sequences in the database, we speculate that it could have been laterally acquired from GGS. Horizontal transfers between GGS and GAS may be ongoing.