A total of 400 clinical Streptococcus pneumoniae strains from patients with respiratory diseases were collected from January 2002 to December 2005. In this study, an increased prevalence of penicillin-nonsusceptible S. pneumoniae (PNSP) from 63% in 2002-2003 to 69% in 2004-2005 was found. During 2004-2005, 56% were erythromycin-nonsusceptible S. pneumoniae (ENSP) and 54% were both PNSP and ENSP. The PNSP, ENSP and PNSP+ENSP groups showed similar trends, ie, sensitive to amoxicillin/clavulanate (range 97.2-98.5%), levofloxacin (range 90.7-92.4%), ceftriaxone (range 87.1-89.4%), and ofloxacin (range 64.8-66.1%). Lower levels of susceptibility were detected for azithromycin, clarithromycin, cefdinir, cefprozil, clindamycin, co-trimoxazole, chloramphenicol and tetracycline in penicillin and erythromycin-nonsusceptible strains. Of the macrolide-resistant S. pneumoniae, 55% of strains exhibited the M phenotype and 45% the constitutive MLS(B) phenotype. No pneumococci with the inducible MLS(B) phenotype were detected in Thailand.