The use of tampons and surgical gauze pads and colonization with Staphylococcus aureus have been established as risk factors for the development of toxic shock syndrome. To elucidate the role of blood factors in the mediation of staphylococcal adherence to fibers used in tampons and surgical packing, an adherence assay with cotton fibers was developed. Results demonstrated that cotton disks precoated with fibrinogen in the presence of human serum albumin bound a significant percentage of the inoculum for both staphylococcal strains tested when compared to human serum albumin controls. Likewise, fibers pretreated with plasma or defibrinated blood containing a small amount of fibrin revealed comparable staphylococcal adherence to that of fibrinogen. In contrast, fibers pretreated with serum, fibronectin, or vitronectin did not exhibit significant augmentation in staphylococcal attachment in comparison to human serum albumin controls. The attachment of staphylococci to fibrinogen and/or fibrin appeared to be specific and is blocked by goat anti-human fibrinogen antibody, but not fibronectin, vitronectin, or nonimmune goat IgG. Thus, our data indicate that fibrinogen/fibrin is the dominant blood component in the mediation of staphylococcal adherence to fibers used in tampons and surgical gauze pads.