Antibodies are known to be an important defence mechanism of the host's immune response towards certain invading microorganisms. Earlier findings have shown that antibodies directed to certain surface molecules on Staphylococcus aureus are of importance in systemic defence against infections. To further investigate the contribution of humoral immunity during intravenously induced S. aureus septicemia and arthritis we have studied the impact of IgG Fc receptors (FcgammaRs). DBA/1 mice deficient for the common gamma-chain (lacking the activating receptors, FcgammaRI, FcgammaRIII and FcepsilonRI) or the inhibitory FcgammaRII and corresponding littermate controls were used. We found that absence of FcgammaRII expression significantly increased the survival rate following severe infection with S. aureus. The FcgammaRII-/- infected mice showed increased levels of IL-10, elevated serum levels of IgG antibodies against clumping factor A and enhanced phagocytic capacity of granulocytes and monocytes, as compared to control mice. Deficiency in the common gamma-chain (FcgammaRI, III and FcepsilonRI) did not influence the arthritogenicity nor the mortality of systemic S. aureus infection. We conclude that expression of Fcgamma receptor II is of importance during S. aureus infection.