At the Ann Arbor Veterans Administration Medical Center, 30 patients over a 6-month period became nosocomially infected or colonized by methicillin-resistant Staphylococcus aureus. Immediate institution of strict infection control measures, in conjunction with surveillance cultures of personnel and treatment of carriers, did not limit spread of the outbreak strain of MRSA. Multiple nonoutbreak strains, phenotypically exhibiting heteroresistance, were also uncovered. Thirteen hospital personnel were identified as MRSA carriers. Trimethoprim-sulfamethoxazole (TMP-SMX) and rifampin initially eradicated the carrier state, documented by anterior nares cultures in 13 courses of treatment in 11 employees. However, three employees were recolonized, one at one month, one at both one and four months, and one at four months. Treatment of the carrier state reservoir among personnel appeared to have no effect on the emergence and spread of nosocomial MRSA.