The activity of a new macrolide, TE-031 (A-56268), against Legionella pneumophila in vitro was superior to the activities of roxithromycin, erythromycin and josamycin. The tissue concentrations of TE-031 in guinea pigs after oral administration (20 mg/kg) was much higher than those of roxithromycin, erythromycin and josamycin. The maximum concentration of TE-031 was 107.0 mg/kg in the lung, and 1.4 mg/l in the serum. The uptake of macrolides by cells collected by bronchoalveolar lavage in guinea pigs was measured by a radioisotopic method. The maximum ratios of intracellular to extracellular concentration of TE-031, roxithromycin, josamycin and erythromycin were 71.9, 24.8, 39.7 and 7.9, respectively. In infected guinea pigs, with the exception of erythromycin, the ratios were reduced to approximately half the values in normal animals. TE-031 showed greater therapeutic efficacy against experimental L. pneumophila pneumonia than roxithromycin, erythromycin and josamycin. TE-031 is a promising drug for treatment of legionella pneumonia and should be investigated in a clinical study on human Legionnaires' disease.