It is now generally accepted that adherence of microorganisms to various components of cardiac valve surfaces is an important early event in the pathogenesis of infective endocarditis. Several lines of evidence suggest that fibronectin may have a role in this adherence process. Fibronectin is an important component of the extracellular matrix of endothelium and fibroblasts and is exposed when these tissues are injured. Fibronectin binds to platelets and fibrin and thereby contributes to the thrombogenicity of surfaces. Because the structure of fibronectin consists of multiple functional domains, fibronectin can bind simultaneously and specifically to microorganisms and various tissue elements such as collagen and cells and may facilitate the uptake of microorganisms by endothelial cells and fibroblasts. Subinhibitory concentrations of certain antibiotics interfere with the expression of bacterial fibronectin receptors and inhibit the binding of Staphylococcus aureus to collagen matrices; this interaction may have implications for antibiotic prophylaxis of infective endocarditis.