To determine how hypoxia may alter determinants of pulmonary transvascular fluid flux, adult male ferrets were exposed to either room air (C) or hypoxia (H; FIO2 = 0.12) for 24 h. After anesthesia and ventilation with C or H, the mean pulmonary artery pressures were 18.4 +/- 2.2 (SEM) and 27.3 +/- 2.9 mm Hg, respectively (p < 0.025). The right lung was then removed for gravimetric analysis of lung water and the left lung was blood-perfused (approximately 142 ml/kg/min) and continuously weighed for 15 min at left atrial pressures of 20, 25, and 30 mm Hg. Filtration coefficient (Kf) was estimated from the slopes of the relationships of rate of weight gain versus change in vascular pressure over the last 5 min of each interval. Extravascular lung water/blood-free dry lung weight for C and H were 2.95 +/- 0.06 (SEM) and 3.53 +/- 0.09 ml/g, respectively (p < 0.01). Kf for C and H were 0.0645 +/- 0.0190 (SEM) and 0.0662 +/- 0.0085 ml/min/mm Hg/100 g, respectively (NS). In a second group of experiments, in which lungs were removed from ferrets after 24 h exposures to C or H, protein reflection coefficients (sigma) were estimated by comparing the increases in perfusate hematocrit and protein concentrations during edema formation. Reflection coefficients for albumin were 0.64 +/- 0.03 (SEM) and 0.39 +/- 0.07 with C and H, respectively (p < 0.01). The sigma values for IgG and IgM were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)