Meticillin-resistant Staphylococcus aureus (MRSA) strain USA 500 predominately colonizes horses and people working with them. Previous studies demonstrate that some Staphylococcus species exhibit higher affinity for corneocytes of specific mammalian species. The objective was to determine the relative affinities of various MRSA strains, meticillin-susceptible S.aureus (MSSA) strains and a meticillin-susceptible Staphylococcuspseudintermedius (MSSP) for equine corneocytes. We hypothesized that MRSA strain USA 500 would exhibit greater adhesion than other staphylococcal strains tested. Epidemic MRSA strains (USA 100, USA 300, USA 500 and USA 800), two MSSA control strains and an MSSP field strain were tested on corneocytes from 15 client-owned horses. Isolates were incubated with corneocytes in conditions (bacterial concentration of 10(8) colony-forming units/mL for 45min) recently shown to maximize adherence of S.aureus without competitive interference. A validated image-analysis system was used to quantify the cell surface density of bacterial adhesion. The MSSP strain adhered with significantly higher affinity (P<0.0015) to corneocytes than did MSSA strains. All MRSA strains other than USA 500 had significantly higher affinity than MSSA strains (P range <0.03 to <0.0015). There were no statistical differences in adhesion between strain USA 500 and the other MRSA strains tested. Meticillin-resistant S.aureus strain USA 500 did not adhere more robustly than other strains of Staphylococcus; therefore, its affinity to colonize horses may not be solely attributed to corneocyte adhesion. Additional studies are required to explain the epidemiological role of this strain as the predominant cause of colonization and infections of horses in North America.