Staphylococcal infection of various prosthetic and internal fixation devices is a major complication associated with orthopaedic surgery. This study investigated the role of the host protein fibronectin in promoting adhesion of Staphylococcus aureus and Staphylococcus epidermidis to metallic surfaces representing materials used for orthopaedic devices. Pure human fibronectin was adsorbed in vitro onto coverslips (0.8 x 0.8 cm) of stainless steel, pure titanium, or titanium-aluminum-niobium alloy. In vitro bacterial adhesion was promoted more strongly by the metallic surfaces coated with fibronectin than by albumin-coated controls for two strains of S. aureus and one strain of S. epidermidis. Furthermore, with the fibronectin-coated coverslips, bacterial adhesion to titanium alloy was significantly greater than adhesion to stainless steel. Adhesion of the three staphylococcal strains was promoted more strongly by coverslips explanted from the subcutaneous space of guinea pigs and tested under similar conditions than by albumin-coated controls. Incubation of either in vitro fibronectin-coated or explanted metallic coverslips with anti-fibronectin antibodies produced a significant decrease in staphylococcal adhesion. These results suggest that the presence of fibronectin on the surface of implanted metallic devices is an important determinant of colonization of orthopaedic biomaterials by staphylococci.