The objective of this study was to investigate the relationship between molecular epidemiology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) over a period of 4 years. The antibiotype of all MRSA isolates that were identified during a yearly period of 3 months was determined; 50 consecutive non-replicate MRSA isolates were typed each year. Susceptibility rates to gentamicin, tobramycin and ofloxacin remained stable (95, 16 and 4 %, respectively). In contrast, the proportion of MRSA isolates susceptible to erythromycin increased progressively from 10.5 to 32.5 % (P < 0.001). PFGE analysis of genomic DNA from 200 isolates revealed the presence of 15 different clones. Two epidemic clones were identified, which contained 150 (clone A) and 28 (clone C) isolates. Non-epidemic strains were more frequently susceptible to ofloxacin (31.8 versus 1.1 %) and tobramycin (45.4 versus 16.8 %) than epidemic strains; those isolates that were susceptible to all antibiotics tested belonged to sporadic clones. The increase of erythromycin susceptibility within MRSA isolates was caused by the emergence of clone C. This study suggests that when selection pressure exerted by an antibiotic is insufficient (i.e. below a threshold level), fitness advantages play a predominant role in the dissemination of MRSA clones. The balance between the selection pressure exerted by antibiotics and the disadvantage of lower replication rates of resistant strains in the absence of antibiotics complicates the biological model of clonal dissemination of epidemic MRSA strains.