From April 1990 to February 1992 two hundred and ten strains of Streptococcus pneumoniae were isolated in the laboratory of Nara Medical University Hospital. Frequency of erythromycin resistant Streptococcus pneumoniae, prescription mode of macrolide antibiotics and biological properties were investigated. 1. Erythromycin resistant Streptococcus pneumoniae was predominantly isolated from the wards of the respiratory unit of Inter- nal Medicine and Pediatrics. 2. Patients with erythromycin resistant Streptococcis pneumoniae were treated with macrolide antibiotics frequently in the respiratory unit of Internal Medicine and Pediatrics. 3. MIC90 of EM, CLDM, MINO and ABPC for Streptococcus pneumoniae was 8.0, 8.0, 8.0 and 1.0 micrograms/ml, respectively, indicating moderate resistance to penicillin derivatives and high resistance to macrolides, particularly EM; some strains showed high levels of MIC over 400 micrograms/ml. 4. Investigations on biological properties using VITEK GPI cards revealed that some erythromycin resistant strains showed less responsiveness to DEX, LAC, PUL and MEL. 5. The survival rate of mice infected with erythromycin resistant strains was longer than that with erythromycin sensitive strains. These findings suggested that the prolonged administration of erythromycin causes a virulence reduction of the organism.