A substantial portion of recently isolated, multiply-resistant Staphylococcus aureus was shown to carry R-determinants in plasmids. Some of these plasmids were small (3 Mdal) and carried only one R-marker. Others were 18-36 Mdal in size and carried two or more R-determinants. Several of the larger plasmids could be transferred by a conjugation-like process. The location of R-markers on transposable DNA sequences also was observed. Transposition as well as stable integration of R-plasmids into the chromosome can explain the frequent observation of chromosomal location of resistance. Chromosomal resistance might be an advantage for an organism frequently exposed to antibiotics. Molecular evidence suggests that methicillin resistance resides on additional chromosomal DNA. The organization of staphylococcal genomes as well as efficient transfer processes explain the genetic versatility of Staph. aureus, which has resulted in the development of multiply-resistant strains.