The antimicrobial susceptibility to ten antibiotics of 197 staphylococcal isolates recovered over a 10-year period from patients with vascular catheter-related bacteremia was examined. Isolated organisms induced methicillin-sensitive Staphylococcus aureus (95 isolates), methicillin-resistant S. aureus (42 isolates) and methicillin-resistant S. epidermidis (60 isolates). A microtiter assay was used to determine the MIC and MBC of individual antibiotics and to conduct time-kill studies of certain drug combinations. The activity of clidamycin, cefamandole and oxacillin was generally restricted to methicillin-sensitive organisms, whereas daptomycin, novobiocin, teicoplanin and vancomycin exhibited bactericidal activity against all tested staphylococcal species. Bacterial resistance to ciprofloxacin was detected among the more recent isolates of methicillin-resistant staphylococci. Minocycline and rifampin demonstrated bacteriostatic and bactericidal activity, respectively, against all groups of organisms. The interaction of rifampin with minocycline, vancomycin, or novobiocin was generally indifferent. The results of this study support the ongoing efforts for evaluation of the antimicrobial efficacy of vascular catheters coated with the combination of minocycline and rifampin.