We examined the changes in vascular and interstitial mechanics in pulmonary emphysema (PE) using a canine lobar model. PE was produced in the left lower lobe (LLL) of five dogs (group E) by six weekly intrabronchial instillations of the enzyme papain. In five control dogs (group C), a normal saline solution was used. In our in vivo preparation, vascular flow (Q) to the LLL was measured. Inflow (Ppa) and outlow (Pv) pressures to the LLL could be varied independently. The relationship of Ppa to Q was examined in zones 2 and 3 of West. The slope of the Ppa-Q relationship was used to determine vascular conductance, whereas the extrapolation to zero flow in zone 2 conditions represented the mean pressure required for vascular recruitment (Pi). Lobar weight gain was measured continuously. Following step increases in Ppa, the rapid increase in wet weight measured when Q to the LLL was zero was used to obtain vascular compliance (C). Subsequent slow increases in wet weight were used to determine the rate of fluid exchange with the interstitium (Qf). The slope of the Qf-Ppa relationship represented fluid conductance (Kf). The extrapolation to zero Qf gave the minimal pressure required for continuous edema formation (Pm). Compared with group C, vascular conductance (G) decreased and Pi increased in group E, whereas fluid conductance (Kf) and Pm increased. The decrease in G most likely resulted from the loss of vascular cross-sectional area in emphysematous lungs, whereas the increase in Pi was possibly due to mechanical changes in the lung interstitium which increased vessel closure. We propose that the increase in Kf in group E reflected an increase in interstitial conductance, such that due to structural changes in the interstitium in emphysematous lungs, tissue resistance to fluid flux decreased.