PURPOSE: Streptococcus pneumoniae is a normal flora and common pathogen of the upper respiratory tract. S. pneumoniae infections are estimated to cause not only localized infection such as pneumonia, and otitis media, but also systemic infections, for example meningitis, sepsis, and so on. Recently, the resistance of S. pneumoniae to penicillin and multidrug has been rapidly increasing in many other parts of the world. So strategies for treating S. pneumoniae are of concern. In this article, we reviewed the efficacy of antibiotics against multidrug-resistant S. pneumoniae infection in childhood. METHODS: Medical records of children who had infections from penicillin-resistant S. pneumoniae admitted to Severance Hospital between January 1997 and December 1998 were reviewed. The patients with congenital heart disease or malignancies were excluded to rule out other factors except antibiotics. We reviewed the efficacy of antibiotics, loss of fever, and duration of improvement of the general condition. RESULTS: The median age of children was four years old. There were 20 cases of localized infections such as pneumonia, otitis media(66.7%), and 10 cases of systemic infections such as meningitis, sepsis(33.4%). Sixty three % of patients were treated with penicillin, thirteen % with 3rd cephalosporin, and twenty three % with vancomycin. Stastically no significant difference was found between these three groups(P=0.85). CONCLUSION: In this study, antibiotics didn't significantly influence the treatment of multidrug- resistant S. pneumoniae infections. The treatment of many patients with congenital heart disease or malignancies was complicated. This suggests that general conditions of patients, such as immunity, is more important than antibiotics in treating the multidrug-resistant S. pneumoniae infection.