Due to its safety profile and ease of oral administration, linezolid became an alternative to vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of our study was to compare bone tissue and plasma concentrations of linezolid and vancomycin in prosthesis-related MRSA infection in a rabbit model.During implantation of titanium cylinders into the femurs of nine rabbits, a bacterial suspension of MRSA was added to induce infection. Antibiotic treatment was started eight hours later. Antibiotic concentrations in plasma (day one, three and seven) and bone (day seven) were determined by HPLC analysis.At steady state the mean peak and trough plasma levels of linezolid were 29.0 microg/mL and 8.2 microg/ mL and for vancomycin 39.1 microg/mL and 28.2 microg/mL. On day seven the mean peak concentration of linezolid in plasma was 28.5 microg/mL and after six hours 26.3 microg/mL and for vancomycin 53.8 microg/mL and 29.1 microg/mL after six hours. Vancomycin showed a penetration into the infected bone (femur) of 53% of plasma concentration, into the uninfected 28%, linezolid 11% (for both six hours after administration).In conclusion, we observed a higher rate of tissue penetration for vancomycin than for linezolid into femur bone in this animal model. As linezolid offers the option for oral treatment of gram-positive organisms, results of further studies comparing vancomycin and linezolid are keenly awaited.