Mucociliary dysfunction results in mucus accumulation, airway obstruction, bacterial colonization, recurrent infective exacerbations, and an increase in morbidity and mortality. Studies in patients with cystic fibrosis, established that inhalation of hypertonic saline (HS) increases clearance of mucus acutely in a dose-dependent manner. Clearance over 90 min was 23.8 +/- 4.0% and 26.0 +/- 3.1% in response to 7% and 12% saline, which was significantly enhanced compared to 12.7 +/- 1.4% and 19.7 +/- 3.1% in response to 0.9% and 3% saline. Mannitol (approximately 300 mg) inhaled as a dry powder had a marked acute effect in patients with bronchiectasis. Clearance over 75 min was 34.0 +/- 5.0% with mannitol, 17.4 +/- 3.8% with control, and 11.7 +/- 4.4% at baseline. Further studies in patients with bronchiectasis showed that mannitol reduces the 24-h retention of radiolabeled mucus, suggesting that the effect of mannitol extends beyond the acute phase. Mannitol helped patients to clear mucus within 2 h that would have taken 24 h to clear without mannitol. A further study in CF patients showed that mannitol was equally effective as 6% HS at improving ciliary and cough clearance. The total clearance over 120 min with mannitol (27.6 +/- 3.7%) and with HS (31.0 +/- 5.5%) was significantly increased compared to their respective controls (18.6 +/- 3.8% and 20.9 +/- 3.6%). These preliminary results suggest that long-term treatment with HS or mannitol may benefit patients with mucociliary dysfunction.