Infants at day care centers tend to contract repetitive upper respiratory infections and prolonged otitis media. The increase in antimicrobial-resistant bacteria, particularly in infants, has given rise to a stubborn therapeutic problem. We studied the nasopharyngeal carriage and drug resistance to Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S. pneumoniae), the most common pathogens of upper respiratory infections, in infants at day care centers. Nasopharyngeal cultures of infants between the ages of 0 and 6 years were conducted at two day care centers in July 2004 ("summer"; n=183), and in February 2005 ("winter"; n=182). Isolated H. influenzae and S. pneumoniae were subjected to antibiotic susceptibility tests by broth microdilution. We also conducted an otolaryngological examination and a survey on past and life histories. H. influenzae in summer (38.3%) increased significantly in winter (57.7%). Beta-lactamase-negative and positive ampicillin-resistant H. influenzae (BLNAR+ BLPAR) in summer decreased significantly in winter. S. pneumoniae did not differ in summer (42.1%) or in winter (43.4%). Penicillin-resistant and intermediate S. pneumoniae (PRSP+PISP) was 41.3% in summer and decreased significantly to 19.0% in winter. BLNAR + BLPAR and PRSP + PISP differed with the day care center. In otolaryngological examination, rhinosinusitis was commonest (28.4% in summer and 30.8% in winter), followed by allergic rhinitis (8.7% in summer and 6.0% in winter) and otitis media (8.2% in summer and 6.0% in winter). Tonsillitis was minor (0.5% in both seasons). Rhinosinusitis in winter was significantly higher in carriers of H. influenzae and/or S. pneumoniae than in non carriers (36.4% versus 16.0%). Breast-fed infants tended to have less otitis media than bottle-fed infants (38.2% versus 52.9%). H. influenzae and/or S. pneumoniae plateaued (75-80%) after 12 months in day care centers. These results suggest that infants attending day care centers are immediately colonized by H. influenzae and S. pneumoniae in the nasopharynx after entering the centers. Nasopharyngeal drug-resistant H. influenzae and S. pneumoniae varied during the seasons and between day care centers. Further prospective studies are needed to determine upper respiratory tract infection in infants at day care centers and to evaluate carriage, epidemiology, and the drug-resistance rates of these pathogens.