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 micro g/ml, and the MIC at which 90% of the isolates were inhibited was 0.06 micro g/ml; the corresponding values for telithromycin were </=0.015 and 0.25 micro g/ml, respectively. For six quinupristin-dalfopristin-resistant strains, the cethromycin MICs were 0.25 to 16 micro g/ml and the telithromycin MICs were 1 to 4 micro g/ml. However, there was only 0.3% resistance to telithromycin.