Methicillin-resistant Staphylococcus aureus (MRSA) is endemic in teaching hospitals in eastern Australian states, with prevalence rates averaging 25-30% of all S.aureus. Between 1990 and 1995, 1467 non-duplicate MRSA isolates from clinically infected sites were tested in Sydney, Melbourne, and Brisbane as part of a national survey of staphylococcal susceptibility. We reviewed the differing evolution of resistance to ciprofloxacin, rifampicin, and fusidic acid. Despite similarities in community and hospital antibiotic use and MRSA prevalence rates, trends in resistance to the oral antibiotics in these cities have progressed independently of each other. In the 1995 survey in individual hospitals in Melbourne, 16-24% of strains were ciprofloxacin-resistant, compared with 80-100% in Sydney and 30-44% in Brisbane. There was great diversity of phage type patterns for ciprofloxacin-resistant strains, suggesting heterogeneous development of resistance. Rifampicin resistance was more closely associated with distinct dominant epidemic phage types, common to institutions in the same city, but without spread to the other cities. Between 1990 and 1995, these comprised 30-60% of all MRSA in Brisbane, compared with 5-10% in Melbourne and < 25% in Sydney. Fusidic acid resistance was uncommon and sporadic (< 5%), and was distributed equally between methicillin-resistant and methicillin-susceptible strains. Resistance to the oral agents in MRSA is due to a complex mix of antibiotic selection pressures and cross-infection with local and epidemic strains in closely related institutions. Each of these mechanisms can predominate, dependent on local factors and the antibiotics used.