All of the methicillin-resistant Staphylococcus aureus (MRSA) strains exhibit resistance to oxacillin by producing PBP2a encoded by mecA, whereas methicllin-susceptible Staphylococcus aureus (MSSA) strains do not. To investigate phenotypic differences other than oxacillin resistance level in responses to oxacillin between MSSA and MRSA, we compared alterations of viability and ultrastructure of MSSA by oxacillin treatment with those of MRSA. When MSSA and MRSA strains were exposed to oxacillin of their respective MICs, and then were assayed for viability and observed by transmission electron microscope, increase in thickness of cell wall was more prominent in MRSA strains than in MSSA strains, while decrease in number of surviving cells was more evident and change in morphology of growing cross wall was greater in MSSA strains than in MRSA strains. It is assumed that these different responses to oxacillin between MSSA and MRSA strains may be due to activation of some PBP2a unbound to oxacillin. In conclusion, MSSA and MRSA showed different functional and morphological responses to oxacillin, although they were treated with oxacillin of concentrations that respectively inhibit their proliferation.