Bacteria increasingly resistant to antibiotics are a major treatment concern of respiratory tract pathogens in children. The aim of this study was to assess the trends of resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to several classes of antibiotics in children<16 years of age and to compare its prevalence with surrounding countries. We studied retrospectively the susceptibility of respiratory tract pathogens isolated from specimens collected from patients at the Geneva Children's Hospital between 1989 and 2004. The susceptibility of S. pneumoniae to penicillin decreased from 98% to 58% (P<0.001) within 16 years, mainly due to strains intermediately resistant (MICs 0.12-1.0 microg/ml). Also erythromycin-susceptible pneumococci decreased from 97% to 63% (P<0.001). The susceptibility of H. influenzae to amoxicillin also significantly declined (87% vs. 82%, P<0.001), and the susceptibility of M. catarrhalis to this drug almost disappeared (29% vs. 5%, P<0.001). However, in 2004 these two bacteria remained 100% susceptible to amoxicillin-clavulanic acid, second and third generation cephalosporins. Invasive H. influenzae strains were significantly more resistant to ampicillin than non-invasive strains, but no susceptibility difference between invasive and non-invasive S. pneumoniae was determined.