The activities of two new macrolides, azithromycin and clarithromycin, were compared in an aerosol-infected guinea-pig model of legionnaires' disease. The results of this study indicate that a low oral dose of azithromycin (3.6 mg/kg) administered once daily gives 100% survival in Legionella pneumophila-infected animals. An eight-fold higher dose of clarithromycin (28.8 mg/kg) given twice-daily was required to achieve the same effect. Similarly, azithromycin was more effective than clarithromycin in preventing pyrexia and in reducing numbers of bacteria and lesions in the lung.