Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become an important problem with increasing frequency. In order to learn if plasmid pattern analysis can be used in epidemiologic investigations of MRSA infections, the authors did plasmid extractions of 70 MRSA stock isolates using a rapid lysostaphin lysis method. All isolates carried at least one plasmid. Most of the isolates had one large plasmid of 24-28 megadaltons (Md). Many also carried one or two small plasmids. Accordingly, 12 different patterns were identified. From these background results, we applied this method to the investigation of two small nosocomial outbreaks of MRSA infection. It was found that the analysis of plasmid pattern and restriction endonuclease analysis are more discriminative than antibiograms. Strains with the same antibiograms can be different by plasmid analysis. It is concluded that the plasmid pattern with a restriction endonuclease analysis study is a reliable method for epidemiologic study of MRSA infections.