Bacterial adherence to polymer surfaces is a required early step in intravenous (iv) device infection. We collected eight strains of Staphylococcus aureus and 19 of coagulase-negative staphylococci from patients with proven iv device bacteremia and studied the role of plasma or connective-tissue proteins in promoting bacterial adherence to polymethylmethacrylate (PMMA) coverslips. Although only a negligible percentage of organisms adhered to albumin-coated PMMA, surface-bound fibronectin significantly promoted adherence of all isolates. Fibrinogen markedly promoted adherence of all S. aureus strains but of only four coagulase-negative strains. Thus, coagulase-negative staphylococci revealed a marked heterogeneity in adherence to fibrinogen-coated surfaces, a result suggesting the existence of heretofore unknown receptors for fibrinogen. Laminin promoted adherence of staphylococci to a much lower extent. Although strain specific, adherence of clinical staphylococcal isolates to foreign surfaces is significantly increased by fibronectin, fibrinogen, and laminin, an observation suggesting the possible contribution of these proteins to the pathogenesis of iv device infection.