Broth microdilution tests were carried out with 2,671 respiratory tract isolates from 19 medical centers throughout the continental United States. The tests compared a streptogramin (RP59500) to erythromycin, dirithromycin, clarithromycin, and azithromycin against Streptococcus pneumoniae, S. pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Against macrolide-susceptible strains, the potency of RP59500 was similar to that of the macrolides: the azalide, azithromycin, was two to four times more potent against H. influenzae. The azalide and three macrolides showed nearly complete cross-resistance. At 2.0 micrograms/ml or less, the streptogramin, RP59500, was active against both macrolide-resistant and -susceptible strains of S. pneumoniae (MIC for 50% of the strains tested, 0.25 microgram/ml; MIC for 90% of the strains tested, 0.5 microgram/ml).