Highly methicillin-resistant Staphylococcus aureus (H-MRSA, MIC greater than 100 micrograms/ml) was prevalent from 1986 in our institution. The failure of povidone-iodine to reduce the prevalence of MRSA led us to choose chlorhexidine-ethanol solution as an antiseptic, and then the isolation frequency of H-MRSA decreased significantly in 1988. When H-MRSA began to increase again recently, we studied the resistance to antiseptics of MRSA in order to investigate the cause of this re-increase. Common antiseptics were tested against 45 strains of H-MRSA and 22 strains of methicillin sensitive S. aureus (MSSA, MIC less than 12.5 micrograms/ml). Dilute preparations (1:100) of povidone-iodine and chlorhexidine-ethanol solution were more effective on H-MRSA than the other antiseptics. Though there was no significant difference between H-MRSA and MSSA in their sensitivity to povidone-iodine, the killing of H-MRSA strains was more delayed than the killing of MSSA strains in chlorhexidine. Even after a 120-second exposure, 13.3% of H-MRSA strains were resistant to chlorhexidine (more than 1000 colonies were recovered). These highly chlorhexidine-resistant strains have been isolated since 1987 when we chose chlorhexidine-ethanol solution as the antiseptic in our institution. Therefore we suspect that the acquirement of resistance to antiseptics by H-MRSA caused the re-increase of this strain.