Neutrophils are regarded as the body's first line of defense against S. aureus invasion and a critical determinant in infection outcome. This interpretation may however represent an over simplification. Studies now challenge the existing dogma surrounding the role-played by neutrophils during S.aureus infections and suggest that under some conditions too many neutrophils maybe detrimental to the host and actually exacerbate the infection. Although not traditionally regarded as an intra-cellular pathogen, numerous studies demonstrate the ability of S.aureus to survive for significant periods of time inside various cell types. Recently we have demonstrated that heightened neutrophil recruitment is associated with increased disease pathogenesis in a murine model of S.aureus surgical wound infection. Decreased bacterial burden was associated with reduced production of CXC chemokines locally at the infection site and reduced infiltration of neutrophils. Administration of CXC-chemokine blocking antibodies during S.aureus challenge decreased infection levels. Furthermore, administration of CXC chemokines directly to the infection site increased the intra-cellular survival of S.aureus within the neutrophils isolated from the infection site. We are currently investigating the critical inflammatory mediators that facilitate intra-cellular survival of S.aureus within neutrophils. It is clear that the absence of neutrophils would lead to overwhealming disease however; our data suggests that CXC chemokine production and neutrophil recruitment to the S.aureus infection site must be tightly regulated. If even a very small number of S. aureus organisms can survive within the neutrophil and begin to replicate, this could lead to severe exacerbation of the infection.