Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether. the chlorhexidine MIC for methicillin-resistant S. zaureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is relevant. In addition, the link between resistances to chlorhexidine, gentamicin, and "nucleic acid-binding" compounds (NAB; which code, in particular, for propamidine 'sethionate and ethidium bromide) requires clarification. We performed chlorhexidine MIC and rate of kill tests on a number of MSSA and MRSA isolates. Two gentamicin-resistant MRSA isolates without NAB plasmids were more susceptible (0.25 and 0.5 ,ug/ml) than four of eight MSSA that we tested (range, 0.25 to 2 ,ug/ml). Chlorhelidine MICs were higher (4 to 8 ,ug/ml) for seven distinct MRSA isolates with plasmids conveying resistance to gentamicin and NAB (GNAB). Curing of the GNAB plasmid from MRSA strains resulted in a fall in the MIC (1 to 3.3 ,ug/ml), but no consistent fall in killing by chlorhexidine was observed. No effect on the chlorhexidine MIC or killing was observed when we cured strains of methicillin resistance. GNAB plasmid transfer resulted in a rise in the chlorhexidine MIC for the strains but no consistent fall in killing by chlorhexidine. Ethical approval was granted for 10 volunteers to each have a methicillin-susceptible, GNAB-resistant, derived transcipient and its GNAB-susceptible isogenic parent applied to separate sites in an in vivo skin test; no significant difference was seen in survival rates after the application of chlorhexidine. These results suggest that chlorhexidine appears to be as effective as a hand-washing agent for MRSA isolates with or without NAB plasmids as it is for MSSA isolates.Nosocomial infection with mnethicillin-resistant Staphylococcus aureus (MRSA) has become a major problem worldwide, and certain MRSA strains-may possess an epidemic potential (EMRSA), although it is unclear what factors are involved (7). Particular EMRSA isolates from the southeast of England (in this report they are termed EMRSA) and Australia (7, 21) appear to be very similar if not identical and possess plasmids with genes coding for resistance to gentamicin, propamidine isethionate, and nucleic-acid binding (NAB) compounds (e.g., ethidium bromide) and, hence, are often termed GNAB plasmids (10).Guidelines (3) published previously to control MRSA have recommended the use of antiseptics to reduce the MRSA load on superficial colonized sites. Chlorhexidine, in particular, has become a controversial choice because of reports of elevated MICs for MRSA strains compared with those for methicillin-susceptible S. aureus (MSSA) strains. Brumfitt et al. (5)