We previously reported that long-term administration of macrolides (MCL) reduced the number of lymphocytes in bronchoalveolar lavage fluid (BALF) of patients with chronic lower respiratory tract disease. To investigate the anti-inflammatory activity of macrolides, we evaluated their effect on apoptosis of lymphocytes isolated from human peripheral blood. Lymphocytes treated with clarithromycin, azithromycin and josamycin at a final concentration of 200 mug/ml showed positive staining for Annexin V, Fas and Fas ligand using flow cytometry with time at 12-72 h, while other antibiotics did not. Our results suggest that macrolides induce apoptosis of lymphocytes through Fas-Fas ligand pathway and could potentially reduce the number of lymphocytes in the lungs of patients with chronic lower respiratory tract disease. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.