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Abstract Background and objectives: Colonization of nasopharynx by Streptococcus Pneumoniae can lead to pneumococcal disease. This study was performed to determine the carriage rate of nasopharyngeal S.pneumoniae in adolescents and their antibiotic susceptibility and serotype prevalence in Zahedan, Iran Material and Methods: Nasopharyngeal specimens were obtained from 865 adolescents aged 10-19 years old of eight schools in Zahedan and then assessed by standard procedures to isolate S. Pneumoniae. The serotyping was carried out by latex agglutination test, the minimum inhibitory concentration (MIC) of penicillin, as well as other commonly used antibiotics, was determined by a broth-dilution method. Results: Pneumococci were Isolated from 15.7% [136/865, 95% confidence interval (CI) 12.3-18.9] of total samples. Of 136 samples, 119 isolates are typified by the available antisera which the most frequent ones are 1, 19A, 15C, 9V, 11A and 19F. Ninthythree pneumococcal isolates are sensitive to penicillin. The MIC values of antibiotics tested are (μg/ml): penicillin 0.01-4, cefotaxime 0.01-4, ceftriaxone 0.02-128, chloramphenicol 0.08-32, ciprofloxacin 0.06-16, erythromycin 0.01-128, tetracycline 0.08- 128 and vancomycin 0.02-1. Conclusion: A clear diversity is seen in the serotype distribution of the S. Pneumoniae isolates and most of the antibiotic resistant strains belonge to a few serotypes. Healthy adolescents in Zahedan commonly show pneumococcal carriage and antibiotic resistance. Keywords: Streptococcus Pneumoniae, nasopharyngeal carriage, penicillin resistance, serotype