We studied the efficacy of arbekacin (ABK) against MRSA that were resistant to gentamicin (GM). ABK was fairly active against most of the GM-resistant MRSA strains. Against highly GM-resistant strains, however, ABK was slightly less active than it was against the low level GM-resistant strains. ABK-resistant mutants were isolated from GM-resistant MRSA at a frequency of 10(-4) to 10(-5) when the selection was made with MIC of ABK. But the frequency decreased with higher concentration of ABK or with a use of 1/2 MIC of beta-lactam antibiotics, such as cefazolin, cefotiam, cefamandole or flomoxef, together with ABK. We isolated a ABK-resistant mutant from a laboratory strain MS353/pMS91 which possess a GM-resistant gene on a plasmid. The gene encodes a modifying enzyme, AAC-6'/APH-2". We compared the enzyme activities between the mutant MS353/pMS91M and MS353/pMS91. The mutant strain showed enzyme activity six times as much as the primary strain. This result suggests that the increase of AGs-modifying enzymes was responsible for the ABK-resistance of MRSA.