The activities of quinupristin/dalfopristin (Synercid), erythromycin and azithromycin against 22 Legionella spp. isolates were measured by a microbroth dilution method. The MICs that inhibited 90% of strains tested were 0.5, 0.35, and 0.5 microg/mL for quinupristin/dalfopristin, erythromycin, and azithromycin, respectively. Quinupristin/dalfopristin was only partially active against intracellular L. pneumophila at high (2 microg/mL), but not low (1 microg/mL) concentration. Activity of the drug in a guinea pig model of Legionnaires' disease could not be accurately determined because of drug toxicity for the guinea pig, although there was evidence that the drug has in vivo activity.