The effect of removing pulmonary blood flow on the clearance of excess liquid and protein from the air spaces and interstitium of the normal lung was studied in anesthetized ventilated sheep. To eliminate pulmonary blood flow to one lung, the left pulmonary artery was occluded. Autologous serum (3 ml/kg) with I-125-labeled albumin was then instilled into the left lower lobe. Hemodynamics and lung lymph were measured, and the lungs were removed after 4 h. Alveolar protein concentration over 4 h was used as the index of alveolar liquid clearance. Total lung liquid clearance was measured by the gravimetric method. The percent increase in alveolar protein concentration over baseline was similar between sheep without pulmonary blood flow (33.8 +/- 17.4) and with pulmonary blood flow (31.1 +/- 14.6); thus, alveolar liquid clearance was not changed by the absence of pulmonary blood flow. Also, in the absence of pulmonary blood flow, lung liquid clearance (as percent of instilled) over 4 h was 27.1 +/- 3.8 (n = 7), which was not significantly different from control experiments with pulmonary blood flow (26.4 +/- 7.1, n = 7). In the sheep without pulmonary blood flow, bronchopulmonary anastomotic flow was 41.5 +/- 21.3 ml/min. To further reduce blood flow to the lung, both the left pulmonary artery and the bronchoesophageal artery were occluded, which reduced bronchopulmonary anastomotic flow to the left lung to 12.0 +/- 9.3 ml/min. This further reduction in blood flow did not, however, change alveolar or lung liquid clearance. Even with this low blood flow to the left lung, the removal of I-125-albumin from the lung was not altered. In the absence of pulmonary blood flow, the lung lymph flow increased but still accounted for only 32% of the excess liquid clearance from the lung; thus, more than half of the alveolar liquid transported to the interstitium was cleared from the lung by nonlymphatic pathways. Therefore pulmonary blood flow is not necessary for the removal of excess liquid and protein from the air spaces and the interstitium of the uninjuried sheep lung.