Streptococcus pyogenes is generally an extracellular pathogen that can survive and persist within the host by circumventing the host defense mechanisms. To achieve this, S. pyogenes has developed a number of strategies to circumvent the host immune system (e.g., virulence factors directed to prevent phagocytosis). By use of a murine model of skin infection, it was shown that survival within host phagocytic cells constitutes an additional strategy used by S. pyogenes to evade the host defenses and disseminate. Viable microorganisms were isolated from mouse phagocytic cells after in vitro or during in vivo infection. The capacity of intracellularly located bacteria to establish infection was demonstrated by the efficiency of gentamicin-treated neutrophils isolated from infected mice to transfer infection when injected intravenously into naive mice. The ability of S. pyogenes to exploit the inflammatory response of the host by surviving inside phagocytic cells may constitute an additional virulence mechanism of this pathogen.