Excessive production of sputum is one of the major symptoms in patients with chronic airway diseases. Because endogenous prostaglandins may play a role in the regulation of airway secretions, blockade of cyclooxygenase pathway with indomethacin could decrease respiratory tract fluid and mucus by inhibiting Cl secretion and glandular secretion and by enhancing Na absorption across airway mucosa. To test this hypothesis, we studied the effect of inhaled indomethacin on bronchorrhea in patients with chronic bronchitis, diffuse panbronchiolitis, and bronchiectasis in a double-blind, placebo-controlled fashion. Patients who inhaled 2 ml of indomethacin (1.2 micrograms/ml) three times a day for 14 days showed a decrease in the amount of sputum, from 189 +/- 19 to 95 +/- 21 g/day (p less than 0.001) and an increase in the solid component of sputum without alterations in parameters of systemic inflammatory responses. Although pulmonary function remained unchanged, perceived dyspnea was improved so that Borg's ratio scale was decreased from 7.1 +/- 0.5 to 4.5 +/- 0.4 (p less than 0.01). Adverse effects, including hypotension and bronchoconstriction, were not observed. The reduction of sputum was accompanied by a significant decrease in the concentrations of prostaglandin (PG)E2, PGF2 alpha, thromboxane B2, and 6-oxo-PGF1 alpha in the sputum. Thus, indomethacin inhalation may be of value in reducing bronchorrhea sputum, probably through the inhibition of PG-dependent airway secretions.