We reviewed the records of 20 patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) and 49 patients with methicillin-susceptible S. aureus (MSSA) bacteremia occurring during a 39-month period. Sixteen of the MRSA bacteremias were clinically significant, as were 42 of the MSSA bacteremias. MRSA bacteremia was almost always nosocomial and occurred mainly in very young patients who were often prematurely born and severely compromised by underlying diseases. In contrast patients with MSSA bacteremia were frequently older children who had no underlying disease and acquired their bacteremic illness in the community. The seven patients with nosocomial MSSA bacteremia had characteristics similar to those of the patients with MRSA bacteremia. Fatality rates for patients with clinically significant bacteremia were 50% for MRSA and 2% for MSSA. Treatment of MRSA bacteremia with vancomycin was effective, provided it was begun early. At hospitals with endemic MRSA it may be necessary to use vacomycin in the initial treatment of nosocomial bacteremia in high risk patients until the identity and antimicrobial susceptibility of the bloodstream pathogen can be determined.