Methicillin-resistant Staphylococcus aureus (MRSA) infection is a well-recognized nosocomial infection of increasing incidence. Recent reports have also revealed an increment of community-acquired MRSA (CA-MRSA) infections in people without any risk factors. We reviewed the medical charts of 464 children with S. aureus infections presenting between January 1997 and August 2001, in order to understand the occurrence of CA-MRSA infections in children without any risk factors and to define the spectrum of disease. MRSA made up 74% of community-acquired S. aureus infections (59/80). Among them, patients without identifiable risk factors comprised 29 CA-MRSA infections (36%). The number of patients with CA-MRSA disease increased from 11 of 172 (6%) S. aureus infections between January 1997 and April 1999 to 48 of 292 (16%) between May 1999 and July 2001. Skin and soft tissue infections were the most common presentations of community-acquired S. aureus infections. Bacteremia was the major manifestation of nosocomial S. aureus infections, and osteomyelitis and bacteremia were not infrequently seen in patients with CA-MSSA infections. Only 13 out of 29 patients (45%) with CA-MRSA infections without risk factors received effective antibiotic therapy, while 16 cases were cured by either antibiotics without in vitro activity, or surgical drainage, or both. CA-MRSA isolates were more likely to be susceptible to minocycline, gentamicin, and trimethoprim-sulfamethoxazole, compared to hospital-acquired MRSA isolates. Our data suggest an increasing role of MRSA as a community pathogen in previously healthy children. Infection control strategies for both hospital and community should be re-evaluated.