Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not been any information regarding the effect of ion transport agonists or antagonists on alveolar liquid clearance in the human lung. Therefore, we studied alveolar liquid clearance in the recently resected human lung from patients who underwent surgery for lung cancer. A test solution of 40 ml of isosmolar albumin solution was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air spaces very slowly, the concentration of alveolar protein over 4 h was used to quantify alveolar liquid clearance. Basal alveolar liquid clearance was 12 +/- 2% over 4 h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, and ouabain (10(-3) M), an inhibitor of Na,K-ATPase activity, reduced alveolar liquid clearance by 40 and 49%, respectively (p < 0.005). Terbutaline (10(-3) or 10(-4) M) doubled alveolar liquid clearance to 28 +/- 9% over 4 h (p < 0.05). Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in alveolar liquid clearance. In conclusion, (1) alveolar liquid clearance in the human lung can be markedly reduced by inhibition of apical sodium channel uptake or Na,K-ATPase activity, and (2) beta-adrenergic stimulation markedly increases the rate of alveolar liquid clearance in the resected human lung without pulmonary perfusion.