In eight isolated dog lobes, we examined the change in extra-alveolar perimicrovascular hydrostatic pressure (Pis) due to lung inflation. The vasculature was filled with autologous plasma. Pulmonary arterial and venous lines were connected to a common plasma reservoir. Perimicrovascular volume change (delta Vis), compliance (Cis), and the microvascular filtration coefficient (Kf) were derived from the change in lobe mass over time following a step increase in vascular pressure (Piv). Initially, transpulmonary pressure (PL) was 5 cmH2O and Piv = 0 cmH2O. At constant Piv, two sequential 5-cmH2O increases in PL increased Vis; division of delta Vis by Cis yielded the change in Pis attributable to lung inflation. Cis was 0.035 +/- 0.018 g X cmH2O-1 X g dry mass-1 (mean +/- SD) at PL = 15 cmH2O. Kf was 0.019 +/- 0.023 g X min-1 X cmH2O-1 X g dry mass-1. With inflation from PL = 5 to PL = 10 cmH2O, Pis = -2.15 +/- 1.76 cmH2O; from PL = 10 to PL = 15 cmH2O, Pis = -2.25 +/- 1.50 cmH2O. This perimicrovascular pressure change is very close to the perihilar interstitial pressure change reported by others. Such near equality suggests that the stress of lung inflation is very uniformly applied to the interstitial continuum.