To study the effect of surfactant administration on fluid balance in the premature lung, we measured pulmonary vascular pressures, lung lymph and pleural liquid flow, and concentrations of protein in lymph, pleural liquid, and plasma before and after birth in 12 chronically catheterized preterm lambs (127-128 d gestation) treated with either placebo or surfactant just before surgical delivery. Eight lambs received intrapulmonary saline (placebo), and four lambs received surfactant; all lambs were mechanically ventilated with O-2 for 8 h after birth. In control lambs, lung lymph and pleural liquid flow increased from 2.7 +/- 0.4 mL/h during the 2-4 h before birth to 9.2 +/- 2.1 mL/h by 6-8 h after birth; lymph and pleural space protein drainage increased from 58 +/- 7 mg/h during the 2-4 h before birth to 134 +/- 25 mg/h by 6-8 h after birth. In lambs treated with surfactant, there was no significant increase in lymph and pleural liquid flow after birth (before birth, 2.3 +/- 0.3 mL/h; 6-8 h after birth, 3.4 +/- 0.9 mL/h); likewise, lymph and pleural space protein drainage did not change after birth (before birth, 54 +/- 6 mg/h; 6-8 h after birth, 50 +/- 8 mg/h). Postmortem extravascular lung water was significantly less in lambs treated with surfactant compared with control lambs (control, 6.5 +/- 0.3 g/g dry lung; surfactant-treated, 5.0 +/- 0.2 g/g dry lung). Thus, surfactant administration at birth diminishes transvascular movement of fluid across the pulmonary microcirculation, preserves lung vascular protein permeability, and reduces pulmonary edema in newborn lambs that are delivered prematurely.