L ung fluid is reabsorbed rapidly at birth to permit alveolar respiration. We reported previously that expression of aquaporins (AQP) 1, 4, and 5 in rat lung increased just after birth. The hypothesis was tested that the increased AQP expression is associated with increased osmotic water permeability (Pf) between the airspace and capillary compartments. Pf was measured in isolated perfused fetal and newborn rabbit lungs using a pleural surface fluorescence method (Carter, E.P., M.A. Matthay, J. Farinas, and A.S. Verkman. 1996. J. Gen. Physiol. 108:133-142). In response to perfusate osmolality increase from 300 to 600 mosM, initial rates of osmotic equilibration were 1.13+/-0.13 mosM/s at 0-12 h after birth, increasing to 1.52+/-0.19 mosM/s at 12-24 h, and 1.83+/-0.10 mosM/s at 24-84 h. Corresponding Pf values (in cm/s x 10(-2)), computed from d[mosM]/dt and alveolar surface-to-volume ratios, were 1.03+/-0.11 (0-12 h), 1.51+/-0.16 (12-24 h), and 1.88+/-0.09 (24-84 h). Pf was relatively low in prenatal (1.22-1.27, fetal days 29 and 31) and adolescent (1.25+/-0.08, 21-d) rabbit lungs. To test for involvement of molecular water channels, measurements were made of Arrhenius activation energy (Ea), mercurial inhibition, diffusional water permeability (Pd), and AQP expression. Temperature-dependence measurements showed a 25% decrease in Ea for Pf in lungs < 1 d vs. 4 d. Pf was decreased 30% by 0.5 mM HgCl2 in < 1-d lungs and 44% in 4-d lungs. Pd was 1.0 x 10(-)5 cm/s and did not change when Pf was increased by 75%. RNase protection assay showed increased transcript expression in the first 24 h after birth for rabbit isoforms of AQP1 and AQP4. These results provide the first functional data on water permeability in perinatal lung. The increased water permeability after birth may facilitate the maintenance of dry alveoli.