MICs, time-kills, and postantibiotic effects (PAEs) of ABT-773 (a new ketolide) and 10 other agents were determined against 226 pneumococci. Against 78 ermB-and 44 mefE-containing strains, ABT-773 MICs at which 50% of the isolates tested were inhibited (MIC 50 s) and MIC 90 s were 0.016 to 0.03 and 0.125 g/ml, respectively. Clindamycin was active only against macrolide-resistant strains containing mefE (MIC 50 , 0.06 g/ml; MIC 90 , 0.125 g/ml). Activities of pristinamycin (MIC 90 , 0.5 g/ml) and vancomycin (MIC 90 , 0.25 g/ml) were unaffected by macrolide or penicillin resistance, while ␤-lactam MICs rose with those of penicillin G. Against 19 strains with L4 ribosomal protein mutations and two strains with mutations in domain V of 23S rRNA, ABT-773 MICs were 0.03 to 0.25 g/ml, while macrolide and azalide MICs were all >16.0 g/ml. ABT-773 was bactericidal at twice the MIC after 24 h for 8 of 12 strains (including three strains with erythromycin MICs greater than or equal to 64.0 g/ml). Kill kinetics of erythromycin, azithromycin, clarithromycin, and roxithromycin against macrolide-susceptible strains were slower than those of ABT-773. ABT-773 had longer PAEs than macrolides, azithromycin, clindamycin, or ␤-lactams, including against ermB-containing strains. ABT-773, therefore, shows promising in vitro activity against macrolide-susceptible as well as -resistant pneumococci.