Coagulase-negative staphylococci are being implicated as pathogens with increasing frequency and this may in part be due to their development of resistance to a wide variety of antibiotics. Because vancomycin is the only drug generally available for treating these multiply resistant organisms, we have tested several combinations of antibiotics for activity in vitro against these organisms. These in-vitro studies suggested that rifampicin combined with either gentamicin or cefamandole might occasionally provide an efficacious alternative to vancomycin, while the novobiocin plus rifampicin combination might be an effective oral regimen against methicillin-resistant coagulase negative staphylococci. Resistance to co-trimoxazole was found in nearly all isolates tested.