Streptococcus pneumonia (pneumonococcus) is a leading human respiratory pathogen that causes a variety of serious mucosal and invasive diseases. There are atleast 90 serotypes of pneumonococcus but it has long been observed that drug resistance is found only in a limited number of pneumococcal serotypes, 6,9,14, 19 and 23. There is no compelling mechanism to explain this restriction. Its ability to develop natural competence for genetic transformation is thought to be a major mechanism for horizontal acquisition and initial development of resistance. It still remains to be elucidated why only few serotypes of S. pneumonia are drug resistance. During this study, it was hypothesized that the serotypes that are commonly associated with drug resistance have higher transformation frequency than the ones that are frequently susceptible. Thus, an in vitro investigation of genetic transformation frequency of these serotypes was compared with the other serotypes (1,3,18,29,33 and 35) 0f s. pneumonia under the influence of the synthetic competence-stimulating peptides to assess their transformation frequency. The transforming DNA was the genomic DNA carrying Tn916-like transposon with the mefE gene that confers erythromycin resistance. The findings suggest that the serotypes-serogroups 6,9,14,19 and 23 that are highly associated with the drug resistance phenotypes do not exhibit a higher degree of transformation efficiency than other serotypes. The serotypes (6,9,14,19 and 23) with highest frequency of resistance are carried in children for a long period of time. Children are more likely to take antibiotics than any other age group. Thus, the serotype association with drug resistance in general is probably due to prolonged exposure to transforming DNA resulting from longer carriage and to a greater selective pressure from antimicrobials.