The Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) is a surveillance study established in 2004 to monitor the activity of tigecycline, the first glycylcycline, and comparator agents [beta-lactams (including penicillins, cephalosporins and carbapenems), glycopeptides, tetracyclines, fluoroquinolones and oxazolidinones] against Gram-positive and Gram-negative pathogens worldwide. This report examines 1692 isolates of Staphylococcus aureus collected in the continental United States between January 2004 and September 2005. Meticillin-resistant S. aureus (MRSA) accounted for 52.0 % of isolates. Prevalence of MRSA by state ranged from 12.5 % in New Hampshire to 100 % in Kentucky. All isolates were susceptible to tigecycline, linezolid and vancomycin. In vitro, tigecycline was potent against both meticillin-susceptible S. aureus (MSSA) (MIC(50) and MIC(90)=0.12 microg ml(-1)) and MRSA (MIC(50)=0.12 microg ml(-1); MIC(90)=0.25 microg ml(-1)). Only a single isolate was resistant to three or more antimicrobial classes. Ninety-six isolates (5.7%) were susceptible to the complete antimicrobial panel.