A study was conducted to examine the factors involved in adherence of Staphylococcus aureus to various catheter materials. Staphylococcal adherence to catheters coated with fibrinogen was specific and significantly increased compared with that to control catheters (preincubated in phosphate-buffered saline). The adherence of S. aureus to fibrinogen-coated catheters was blocked by goat anti-human fibrinogen antibody, but not fibronectin, vitronectin, or nonimmune goat IgG. Adherence to catheter tubings coated with fibrin did not differ markedly from that to those coated with fibrinogen alone, suggesting the conservation of the staphylococcal binding domain during the conversion of fibrinogen to fibrin. Plasma proteins such as fibronectin or factor XIII that interacted with fibrin did not modify staphylococcal adherence to fibrin. Adherence studies with staphylococcal cells treated with proteinases revealed that staphylococcal surface protein(s) were responsible for fibrinogen binding. These data indicate that fibrinogen or fibrin is the dominant plasma mediator of staphylococcal adherence to intravascular catheters.