During 1994 and 1995, an increase in the number and severity of group A streptococcal (GAS) infections was noted in North Carolina. Ninety-six patients had GAS recovered from blood and other sterile body fluids, abscesses, and soft tissue. The overall case fatality rate was 11% but was much higher in patients with toxic shock syndrome (55%) and necrotizing fasciitis (58%). Recent invasive GAS isolates were compared with pre-1994 invasive isolates and temporally related pharyngeal isolates by M protein serotyping, pulsed field gel electrophoresis (PFGE), and polymerase chain reaction amplification of the streptococcal pyrogenic exotoxin A gene. Serotypes M1 and M3 accounted for 50% of recent invasive isolates (1994–1995) and 58% of pharyngeal isolates (1994). The latter isolates demonstrated PFGE patterns that were identical to invasive M1 and M3 strains, suggesting that pharyngeal infections may have served as a reservoir for virulent GAS clones.