The population structure of methicillin-resistant Staphylococcus aureus (MRSA) is predominantly clonal, which may be related to the fitness of the genetic background of the methicillin-susceptible S. aureus (MSSA) into which the mecA chromosomal resistant determinant has inserted. To test this idea, we assessed whether the genotypes of New York MRSA are present in MSSA populations by using a combination of protein A gene sequence typing (spa typing) and pulsed-field gel electrophoresis (PFGE). Although about 16% of colonizing MSSA isolated from community subjects were related to MRSA, only one of the five predominant New York MRSA clonal types was found among the MSSA isolates. Similarly, among nosocomial MSSA, only four MRSA homologues were observed, two of which may have arisen through deletion of the mec element. Thus, MRSA clonal types represent a limited spectrum of the diversity seen in community and hospital S. aureus populations. The data are best explained by antibiotic selection pressure, as opposed to increased transmissibility or virulence, being responsible for the clonal dissemination of the resistance phenotype in MRSA genetic backgrounds, an in turn, the limited spread of these strains outside of the hospital environment.