In this study, the antimicrobial resistance profiles of pneumococci isolated from respiratory specimens of patients from Shanghai, China, in 2004 and 2005 are described. Non-susceptible rates to penicillin and erythromycin among paediatric isolates (n=122) were 63.1% and 94.3%, respectively, whilst those of adult isolates (n=39) were 20.5% and 69.2%, respectively (P<0.0001 and P<0.0002). Nineteen serotypes were identified among 103 tested strains, 73.8% of which belonged to 19F, 14, 23F, 6B and 19A. The erm(B) gene was detected in 51 erythromycin-resistant strains (52.6%), the mef(E) gene in 5 strains (5.2%) and both erm(B) and mef(E) in 41 strains (42.3%). Among 45 sequence types (STs) determined by multilocus sequence typing (MLST) in these 103 isolates, 25 STs were new assignments and 9 STs contained 10 new alleles. On the other hand, 46 (68.7%) of 67 penicillin-non-susceptible S. pneumoniae and 51 (52.6%) of 97 macrolide-resistant S. pneumoniae were characterised as belonging to four international resistant clonal complexes, Taiwan(19F)-14, Spain(23F)-1, Spain(6B)-2 and Taiwan(23F)-15. Our findings indicate that the spread of international resistant clones played a predominant role in the emergence and increase of resistance in Shanghai. Conjugate vaccination may be a promising method to prevent the increase in pneumococcal resistance.