An outbreak of methicillin sodium-resistant Staphylococcus aureus (MRSA) infection and colonization, mainly centered in the vascular surgery service, occurred in a 1000-bed tertiary care center between December 1983 and December 1984. Methicillin-resistant S aureus isolated before and during the outbreak was studied by both bacteriophage typing and by restriction endonuclease digestion of bacterial plasmid DNA. Bacteriophage typing was discrepant in nine (56%) of the 17 repeated analyses compared with one (3.4%) of the 29 for plasmid profiling. These typing methods revealed that the epidemic strain was introduced to the hospital from the community 15 months before the outbreak. The outbreak was caused by cross-transmission of the epidemic strain by health care personnel and was controlled by treatment of colonized personnel, education of personnel, and institution of barrier precautions for colonized or infected patients. Plasmid profiling with restriction endonuclease digestion was easier, more rapid, and more specific than bacteriophage typing in the evaluation of this outbreak.