Human mononuclear leukocytes kill Staphylococcus aureus cells in vitro. The killing of the bacteria takes place even in the absence of antibodies. The presence of antibodies (in an autologous inactivated serum) usually enhances the antibacterial activity of mononuclear leukocytes. In some cases, however, this activity is markedly decreased by the serum, probably depending of the spectrum of antibodies contained in the serum. The antibacterial activity of mononuclear leukocytes is mostly due to monocytes because their depletion causes substantial drop or the activity disappearance. We failed to demonstrate in the case of S. aureus the antibacterial cytotoxicity of T lymphocytes described by some authors dealing with Gram-negative bacteria. Large differences in the structure of the bacterial cell wall underlie apparently the different sensitivity of G+ and G- bacteria to some protective mechanisms of the host. In the antibacterial assay against S. aureus, electron microscopy revealed a maximal activation of monocytes which phagocytized the bacteria although extracellular killing is not excluded. Electronoptical findings point also to a possible participation of NK cells in the antibacterial cytotoxicity against S. aureus.