Although many recently produced transgenic mice possess gene alterations affecting pulmonary vascular function, there are few baseline measurements of vascular resistance and permeability. Therefore, we excised the lungs of C57/BL6 mice and perfused them with 5% bovine serum albumin in RPMI-1640 culture medium at a nominal flow of 0.5 ml/min and ventilated them with 20% O₂-5% CO₂-75% N₂. The capillary filtration coefficient, a sensitive measurement of hydraulic conductivity, was unchanged over 2 h (0.33 ± 0.03 ml ⋅ min⁻¹ ⋅ cmH₂O⁻¹ ⋅ 100 g⁻¹) in a control group ventilated with low peak inflation pressures (PIP) but increased 4.3-fold after high PIP injury. Baseline pulmonary vascular resistance was 6.1 ± 0.4 cmH₂O ⋅ ml⁻¹ ⋅ min ⋅ 100 g⁻¹ and was distributed 34% in large arteries, 18% in small arteries, 14% in small veins, and 34% in large veins on the basis of vascular occlusion pressures. Baseline vascular compliance was 5.4 ± 0.3 ml ⋅ cmH₂O⁻¹ ⋅ 100 g⁻¹ and decreased significantly with increased vascular pressures. Baseline pulmonary vascular resistance was inversely related to both perfusate flow and microvascular pressure and increased to 202% of baseline after infusion of 10⁻⁴ M phenylephrine due to constriction of large arterial and venous segments. Thus isolated mouse lung vascular permeability, vascular resistance, and the longitudinal distribution of vascular resistance are similar to those in other species and respond in a predictable manner to microvascular injury and a vasoconstrictor agent.