We examined the effect of instilled perflubron (LiquiVent) on the transport properties of alveolar epithelium in anesthetized rats. Krebs-Ringer bicarbonate (1 to 4 ml) containing (125)I-albumin, [(3)H]mannitol and [(14)C] sucrose was instilled into airspaces either alone (n = 29), or with 1 (n = 21) or 2 (n = 12) ml perflubron and sampled 30 min later. Absorption was deduced from the changes in (125)I-albumin activity per unit volume in the airspace instillate, and changes in [(3)H]mannitol and [(14)C]sucrose activity per unit volume were used to evaluate the passive permeability of the alveolar-airway barrier. The rate of Ringer absorption depended on the volume instilled [0.38 (ml/h)/ml Ringer]. Perflubron (1 or 2 ml) increased Ringer absorption by 0.26 (p < 0. 001) and 0.19 ml/h (p < 0.05), respectively. However, 2 ml perflubron increased absorption less than did the same additional volume of Ringer (p < 0.001). The passive permeability of the alveolar-airway barrier increased exponentially with instilled Ringer volume. Sucrose/mannitol size selectivity was lost when Ringer volume was > 2 ml and albumin leaked from airspaces when it was 4 ml. Instillation of 2 ml perflubron prevented this increase in permeability, but 1 ml did not. No albumin leaked with perflubron even when the total volume of liquid in airspaces (Ringer + perflubron) was > 4 ml. These results suggest that perflubron can be beneficial in pulmonary edema by redistributing the alveolar liquid over a larger surface area, thus accelerating resorption. In addition, larger doses of perflubron may better preserve epithelial permeability during alveolar flooding.