The invasiveness of 96 group A streptococci (GAS) isolates (56 from throat or skin and 40 from blood) were analyzed. GAS invasion strongly correlated with the source of the isolates, whereas no correlation was observed with the Vir type. Isolates from throat or skin exhibited the highest invasion efficiency (57% were between 0.1% and 10%). In contrast, 77.5% of the blood isolates were noninvasive (efficiency <0.01%) and only 7.5% exhibited rates comparable to those of throat or skin isolates (>0.1%). Immunofluorescence studies of 34 selected isolates showed that attachment and invasion are strain-related. Although isolates with high invasiveness usually exhibit high attachment, isolates that showed high attachment and no invasion or poor attachment and efficient internalization were identified. The ability of GAS to invade and survive within eukaryotic cells may provide bacteria a sure niche, in which they are protected against host defense mechanisms or antimicrobial agents favoring their local persistence.