To determine the frequency, serotypes and susceptibility profiles to eight antimicrobials in Streptococcus pneumoniae nasopharyngeal isolates from a representative sample of children under 5 years of age, residents of Mexico City. A cross-sectional survey was conducted in 573 children aged 2 months to 5 years.A nasopharyngeal sample was taken. S. pneumoniae identification, capsular serotyping and antimicrobial susceptibility to eight antimicrobials were performed according to standardized methods. S. pneumoniae was isolated in 122/573 (21.4%) children. The most frequent capsular serotypes were 23F, 35, 19F, 11A and 15A; 46% of isolates corresponded to serotypes not included in the heptavalent vaccine. Low penicillin susceptibility was found in 12% of strains with 3% of highly resistant penicillin strains; erythromycin resistance was >30% and trimethoprim-sulfamethoxazole resistance >40%. None of the isolates was resistant to vancomycin, cefotaxime, amoxacillin-clavulanate, chloramphenicol or ampicillin. Several S. pneumoniae serotypes from nasopharyngeal carriers are not included in the heptavalent vaccine. Resistance to trimethoprim-sulfamethoxazole and macrolides is high. The medical community should be aware of these results.