Alveolar and lung liquid clearances were studied over 1, 4, and 6 h in intact anesthetized ventilated rats by instillation of 5% albumin solution with 1.5 microCi of 125I-labeled albumin (3 ml/kg into 1 lung or 6 ml/kg into both lungs). Alveolar protein clearance as measured by residual 125I-albumin in the lung over 6 h was similar to the slow rates measured in other species. Alveolar liquid clearance was estimated by the concentration of albumin in the air spaces. After 1 h, this concentration was 7.8 +/- 0.7 g/dl, which was significantly greater than the initial protein concentration of 5.3 +/- 0.2 g/dl (P < 0.05). Amiloride (10(-3) M) inhibited 45% of the basal alveolar liquid clearance, and ouabain (10(-3) M), instilled and intravenously infused (0.004 mg), inhibited 30% of the clearance. beta-Adrenergic agonist instillation increased alveolar liquid clearance to the fastest 1-h rate (48 +/- 3% of instilled volume) that we observed in any intact species. The removal of the instilled fluid from the lung (expressed as lung liquid clearance; 0.96 +/- 0.3 ml/h) was twice as fast as the rate of alveolar and lung liquid clearance reported in the isolated or in situ rat lung models. The rate of alveolar and lung liquid clearance in these intact rats was significantly faster than those in prior studies in dogs and sheep and was similar to the rates in rabbits.