Monocytes are important effector cells in the pathogenesis of bacterial endocarditis since they provide the tissue factor that activates the coagulation system and maintains established vegetations. Monocytes secrete cytokines that can modulate monocyte tissue factor activity (TFA), thereby affecting the formation and maintenance of vegetations. In this study, we show that monocytes cultured for 4 h on a Streptococcus sanguis-infected fibrin matrix mimicking the in vivo vegetational surface express high levels of TFA. This was accompanied by secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF-), interleukin-1 (IL-1), and IL-1. After a 24-h incubation period the anti-inflammatory cytokine IL-10 could also be detected. Our data show that, whereas TNF- and IL-1 have a minor role in the induction of TFA by monocytes cultured on a fibrin matrix, TNF- but not IL-1 plays an important role in the induction of IL-10 by these cells. In turn, our data show that IL-10 is an important factor in the downregulation of monocyte TFA. In summary, we conclude that IL-10 is an important factor in the control of monocyte TFA in endocardial vegetations.