Aim: To evaluate the synergistic activity of antimicrobial drugs against lineages of methicillin-resistant Staphylococcus aureus (MRSA) carrying SCCmec IV. The biofilm production and related genes were also detected. Methods and Results: Forty two MRSA isolates were tested for biofilm production and related genes. Biofilm/biomass susceptibility to gentamicin (G), linezolid (L), rifampicin (R) and vancomycin (V) was determined for six isolates from three lineages prevalent in Rio de Janeiro hospitals in concentrations ranging from 0 center dot 25 to 64 mu gml(-1). Biomass was evaluated by microtitre plate test and number of viable cells (CFU cm(-2)) and inspected by epifluorescence microscopy. All isolates presented the icaA and sasG genes, but only 38% were biofilm producers. There were 50 and 45% biomass reductions when concentrations >= 4 mu gml(-1) of R or L and >= 16 mu gml(-1) of G or V, respectively, were used. Synergism tests produced a 55% biomass reduction with R-2 mu gml(1)+G(16 mu gml)(1), R-2 mu gml(1)+L-2 mu gml(1), R-2 mu gml(1)+V-4 mu gml(1), and L-2 mu gml(1)+V-4 mu gml(1). Number of viable cells was reduced from 2 to 3logs with R-2 mu gml(1)+L-2 mu gml(1), and R-2 mu gml(1)+V-4 mu gml(1). Conclusions: Synergisms involving R plus L and R plus V caused important reductions in biofilm/biomass and the number of viable cells. Drug combinations should be considered in the chemotherapies of MRSA-SCCmec IV infections. Significance and Impact of the Study: Biofilms in MRSA infections restrict the clinical choice of antimicrobials. Thus, knowledge of the best options for monotherapy and drug synergisms could improve clinical results.