Streptococcus mutans, a member of the viridans streptococci, is the etiologic agent of dental caries and is also a causative agent of subacute infective endocarditis. The generation of proteolytic molecules, such as plasmin, may be important in the pathogenesis of endocarditis caused by S. mutans. In this study, we demonstrate that S. mutans cells have the ability to bind and activate plasminogen to plasmin. Incubation of S. mutans cells with plasminogen was found to be sufficient for the activation of plasminogen, which suggests the presence of an endogenously produced plasminogen activator. The plasmin activity generated by S. mutans cells was shown to be inhibited by epsilon-aminocaproic acid, lysine, aprotinin, and alpha(2)-macroglobulin. We also show that S. mutans cells have the ability to bind and activate plasminogen from human plasma as well as human serum. The plasmin activity generated on the surface of S. mutans cells could degrade the extracellular matrix molecule, fibronectin. (C) 2004 Elsevier Inc. All rights reserved.