Ten patients with bacteremia due to methicillin-resistant Staphylococcus aureus were treated with vancomycin. These patients were compared with matched controls, nine bacteremic patients with methicillin-sensitive S. aureus, and one patient with penicillin-sensitive S. aureus. Controls were treated with a penicillin. There were no significant differences in time to defervescence, metastatic infections, relapse, mortality, need for surgical drainage, or duration of therapy. Fifteen of 19 episodes of serious methicillin-resistant S. aureus infection responded to vancomycin. Severe toxic effects included tinnitus, neutropenia, rash, and possible nephrotoxicity. Tolerance (a minimal bactericidal concentration to minimal inhibitory concentration ratio of at least 32), but not a minimal bactericidal concentration of at least 32 mg/L, correlated with therapeutic failure (respectively, p = 0.04 and p = 0.11, Fisher's exact test). Bacteremic infections due to methicillin-resistant and methicillin-sensitive S. aureus cause similar morbidity and mortality. Vancomycin is effective but potentially toxic therapy for most serious infections due to methicillin-resistant S. aureus. In-vitro tests may not predict therapeutic efficacy.