Objective To investigate the nasal carriage of antibiotic-resistant pneumococci in children of < 5 years old in the following four cities, Beijing, Shanghai, Guangzhou and Xi' an. Methods A total of 647 pneumococci strains were isolated and detected. Minimal inhibition concentrations ( MICs) of antibiotics were determined by E-test. Disk diffusion test was used for the measurement of antimicrobial susceptibility. Results Prevalence of penicillin non-susceptible Streptococcus pneumoniae in the four cities was 41%, with Guangzhou (60.8%) ranking first, followed by Xi' an (45%), Shanghai (37%) and Beijing (25.9%). The majority of penicillin non-susceptibility isolates (23.9%-53.8%) had a low level of resistance (MIC 0.64-1.5 mug/ml). The most sensitive antimicrobials in terms of percentage of susceptible organisms were amoxicillin-clavulanic acid (99.4%), followed by ceftriaxone (92.1%); cefurxime and cefaclor were slightly more sensitive than penicillin with susceptibility of 74.8% and 77.9%. Erythromycin, tetracycline and TMP-SMZ were highly resistant (83.6%, 82.1% and 76.2% respectively). Among erythromycin resistant isolates, 100% were resistant to azithromycin, 98.6% to clarithromycin, 97.2% to roxithromycin and spiramycin, and 96.6% to clindamycin. 97.2% (141/145) were typical of the macrolides-lincosamides-streptogramons B (MLSB) resistance phenotype, and 2.8% (4/145) were M phenotype. The group of PRSP was with significantly higher rates of non-susceptibility for ceftriaxone (18.4%), cefurxime (58.6%), cefaclor (53.4%), compared with the group of PEN-S (0.5%, 1.8% and 0.2%, respectively) and the rate of multi-drug resistance in the isolates of PRSP group (92.9%) was significantly higher than that of PEWS group (59.2%). Conclusion The rates of penicillin and multi-drug resistance among isolates of pneumococci carried nasally in are high children and the high prevalence of multi-drug resistance in the Chinese population may be becoming one of the most serious problems in this century.