To investigate whether aerosolized gentamicin (GM) prevents myeloperoxidase (MPO)-mediated airway injury and mucus hypersecretion, a short course of aerosol therapy (3 d) with GM 40 mg or 0.45% saline (saline) twice per day was conducted. Twenty-eight patients with bronchiectasis and mucus hypersecretion after adequate chest care and hydration were enrolled in a randomized, double-blind fashion. MPO levels in sputum collected on arising were determined by fluorometric assay at 655 nm before and after treatment. The sputum MPO level significantly decreased in patients receiving aerosolized GM, from 0.22 +/- 0.04 to 0.14 +/- 0.04 U/g (n = 15), but not in patients with saline inhalation (0.23 +/- 0.03 to 0.17 +/- 0.02 U/g; n = 11). The daily sputum amount significantly decreased from 94.6 +/- 21.6 to 58.1 +/- 17.8 ml (n = 13, p < 0.01) in the GM group, whereas it increased from 78.6 +/- 25.4 ml to 120.5 +/- 33.9 ml (n = 11, p < 0.05) in the saline group. The change in the amount of daily sputum was related to that in the sputum MPO level in the GM group (r = 0.61; p < 0.01). Inhalation of GM, but not saline, significantly (p < 0.05) increased the value of peak expiratory flow (PEF) from 186.4 +/- 25.1 to 216.4 +/- 26.4 L/min and decreased the variability of PEF from 24.6 +/- 5.1 to 6.1 +/- 2.3 %. The nocturnal desaturation and the 6-min walking distances were also significantly improved in the GM group (11.2 +/- 3.8 to 0.6 +/- 0.5 min/h; 324.9 +/- 43.1 to 408.1 +/- 25.9 m; p < 0.05; respectively), but not in the saline group. Subjective improvements in the Borg scale and self-sputum assessment were found in the GM group only. In conclusion, aerosolized GM is effective in improving airway hypersecretion and inflammation in patients with bronchiectasis.