Six Latin-American countries participated in an epidemiological surveillance study conducted by the Pan American Health Organization in order to determine the relative prevalence of capsular types and antimicrobial resistance patterns of Streptococcus pneumoniae (SPN) causing invasive infections in children <5 years of age. In Argentina, the incidence of penicillin resistance (PR) was 24.4%, and it was significantly associated with serotype 14 (p < 0.001). The chromosomal DNA of 56 of those SPN isolates, 39 PR and 17 susceptible, was digested with SmaI and resolved by PFGE. Eighty-two percent (32/39) of the PR isolates shared characteristics with the widely spread International Spanish/French clone (clone B). All members of clone B except one expressed serotype 14, with the exception of one isolate that expressed serotype 19F and probably resulted from an in vivo capsular transformation event. Only a single isolate shared features with the 23F International Spanish/USA clone (clone A). The 17 penicillin-susceptible (PS) SPN isolates presented an enormous degree of variation in the chromosomal background, expressing 12 serotypes and 13 PFGE patterns. The data suggest that over 80% of the SPN-PR isolates in Argentina were imported, and this confirms the importance of the geographic spread of SPN clones in South America.