Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.