The activity of the ketolide ABT-773 against 180 erythromycin-resistant Streptococcus pneumoniae obtained from children was compared with telithromycin, azithromycin, clarithromyin, roxithromycin, clindamycin, penicillin, levofloxacin and gatifloxacin. Ketolide MICs were all < or =1 mg/l, with ABT-773 being the most potent of all drugs tested. MIC(90)s for macrolides and azithromycin in mefE+ isolates were 16-32 compared with >128 mg/l for ermB+ isolates. ABT-773 and telithromycin MIC(90)s for mefE+ isolates were 0.125 and 0.5, compared with 0.032 and 0.016 mg/l for ermB+ isolates and 0.5 and 1 mg/l, respectively, for isolates containing both genes. Clindamycin was active against mefE+ but not ermB+ isolates. 155 isolates were resistant to penicillin. All fluoroquinolone MICs were < 1 mg/l. Further studies of ketolides for treatment of paediatric S. pneumoniae infections are warranted.