A large outbreak of infections caused by methicillin and aminoglycoside resistant Staphylococcus aureus provided the opportunity to evaluate mechanisms of resistance and compare the usefulness of typing systems. Between January 1979 and December 1980, 63 patients developed infections with S aureus resistant to multiple antibiotics, including methicillin and tobramycin. All isolates had an identical antibiogram and were phage type 47/54/75/77/83A. Beginning in January 1981, a superimposed outbreak caused by S aureus of the same phage type but with a resistance pattern now including gentamicin occurred. The two strains contained different aminoglycoside inactivating enzymes. The initial strain contained a single plasmid of 21.5 mDa molecular weight, whereas the subsequent strain which had acquired gentamicin resistance contained this plasmid plus a heavier one of 33 mDa. Plasmid analysis complements the analysis of antibiograms and phage types and aids in defining epidemiologic patterns of transmission.