Between October 1985 and August 1986, 49 isolates of methicillin-resistant Staphylococcus aureus (MRSA) were obtained from 26 neonates in the neonatal intensive care unit (NICU) at the Medical University Hospital, Charleston, SC. Sites of MRSA isolation were the respiratory tract (33%); nasopharynx (12%); gastrointestinal tract (12%); eye (8%); blood (6%); and catheter tips, wounds, or umbilicus (29%). Very low birth weight was a significant risk factor for MRSA acquisition. All isolates had the same phage type (47/54/75/83A), antibiogram, and whole-cell protein profile. Agarose gel electrophoresis of all 49 isolates disclosed a plasmid level of approximately 45 X 106 daltons (45 megadaltons) in ten different isolates and no plasmid DNA in 39 isolates. Cultures of NICU personnel failed to disclose MRSA carriers and environmental cultures for MRSA were negative. Ten selected isolates showed lower minimal bactericidal concentrations for hexachlorophene than for chlorhexidine. Standard infection-control measures such as contact isolation, hand washing with chlorhexidine, and cohorting (when possible) failed to contain the epidemic. Ultimately, eradication of MRSA from the NICU was associated with the institution of hexachlorophene hand washing.