In vitro infection of cultured human cardiac valve endothelium (HCVE) with Staphylococcus aureus was used as a model to study potential mechanisms of vegetation formation in infective endocarditis. S. aureus was observed to adhere to and be ingested by HCVE. Infection for 8 h resulted in increased levels of procoagulant activity in HCVE, shown to be tissue factor by a specific assay. Mean activity in infected HCVE was 662 +/- 149 (mU/10(5) HCVE +/- 1 SD) versus 221 +/- 78 in control HCVE; surface-expressed activity was 57 +/- 25 in infected monolayers and undetectable (less than or equal to 10) in controls. Bacteria alone had no activity. These results suggest that endothelium may have a functional role in the pathogenesis of S. aureus endocarditis and may provide one potential mechanism for activating coagulation to initiate vegetation formation on a colonized cardiac valve.