Among young children, pneumococcal nasopharyngeal colonization (NPC) rates of >90% have been described. The aim of our study was to assess the effect of amoxicillin exposure on the NPC. From Dec 2001 to Feb 2004, less than 5 years old children with respiratory symptoms and fever who were prescribed amoxicillin were eligible. Three nasopharyngeal swabs were taken: at the time of the initial visit (IV), 60 hours after amoxicillin discontinuation (end of treatment visit, ETV), and 4 weeks later (follow-up visit, FUV). One hundred and thirty four children were included. NPC was detected in 58.5%, 42.9% and 51% of <1, 1-2 and >2 years-old children respectively (NS). Vaccine serotypes (VS) or vaccine-related serotypes (VRS) were identified in 80%, 40% and 55% of <1-year-old, 1-2 year-old and >2-year-old children respectively (NS). The proportion of PNSSP was 60% in <1-year-old children, 43% in 1-2 year-old children and 40% in >2-year-old children (NS). 49 out of 134 (36.5%) children completed the three study visits. 51%, 22.4% and 46.9% of those were colonized at IV, ETV and FUV, respectively (p=0.007). The percentage of resistant SP was 28%, 45.5% and 8.7% (p=0.05) for penicillin. In children <1 year of age, a higher proportion of SP colonization, presence of VS and PNSSP was found. A downfall of NPC at the end of therapy was observed. NPC returned to baseline levels thanks to "de novo" colonization in half of the cases, a few weeks after.