The in vitro activities of two investigational ketolides, cethromycin (formerly ABT-773) and telithromycin, were determined for a selected group of 312 Streptococcus pneumoniae isolates from a national surveillance program. The MIC of cethromycin at which 50% of the isolates were inhibited was 0.008 mug/ml, and the MIC at which 90% of the isolates were inhibited was 0.06 mug/ml; the corresponding values for telithromycin were less than or equal to0.015 and 0.25 mug/ml, respectively. For six quinupristin-dalfopristin-resistant strains, the cethromycin MICs were 0.25 to 16 mug/ml and the telithromycin MICs were 1 to 4 mug/ml. However, there was only 0.3% resistance to telithromycin.