The distribution and antibacterial susceptibility of macrolide resistance genotypes among 7083 Streptococcus pneumoniae isolates collected worldwide during 2003-2004 from patients with community-acquired respiratory tract infections, including patients within 48h of admission to hospital, were analysed. The overall rate of erythromycin resistance was 37.2% (intercountry range <10% to >50%). The most common resistance mechanism globally was erm(B) (55.0% of erythromycin-resistant S. pneumoniae (ERSP)), followed by mef(A) (30.6%) and erm(B)+mef(A) (12.0%). Genotype distribution varied by age group (P<0.0001); erm(B)+mef(A) was more prevalent (21.8% of isolates) among patients 0-2 years of age than among other age groups (P<0.001). The prevalence of tetracycline resistance among mef(A) isolates varied between different countries. Of the erm(B)+mef(A) strains, 43.5% were resistant to amoxicillin/clavulanic acid. Most ERSP isolates were susceptible to levofloxacin (98.3%) and telithromycin (99.4%).