The response of segmental filtration coefficients (Kf) to high peak inflation pressure (PIP) injury was determined in isolated perfused rat lungs. Total (K f,t ), arterial (K f,a ), and venous (K f,v ) filtration coefficients were measured under baseline conditions and after ventilation with 40-45 cmH(2)O PIP. K f,a and K f,v were measured under zone I conditions by increasing airway pressure to 25-27 cmH(2)O. The microvascular segment K f (K f,mv ) was then calculated by: K f,mv = K f,t - K f,a - K f,v. The baseline K f,t was 0.090 +/- 0.022 ml. min(-1). cm H2O(-1). 100 g(-1) and segmentally distributed 18% arterial, 41% venous, and 41% microvascular. After high PIP injury, K f,t increased by 680%, whereas K f,a, K f,v, and K f,mv increased by 398, 589, and 975%, respectively. Pretreatment with 50 microM gadolinium chloride prevented the high PIP-induced increase in K f in all vascular segments. These data imply a lower hydraulic conductance for microvascular endothelium due to its large surface area and a gadolinium-sensitive high-PIP injury, produced in both alveolar and extra-alveolar vessel segments.