The peribronchovascular interstitium of the lung is a potential space that expands in pulmonary edema with the formation of large liquid cuffs. To study the time course of cuff formation we inflated nine isolated dog lung lobes with liquid to total lung capacity, rapidly froze them in liquid N2 after inflation periods of 1-300 min, then photographed 20 blocks of each lobe at X3 magnification. From the photographs we measured the ratio of cuff area to vessel area for arteries and veins of 0.05-8 mm diam. We found that the cuff-to-vessel area ratio attained a maximum value of 3-4, which was independent of vessel size. However, the first cuffs to reach maximum size were those around vessels of 0.1-0.5 mm diam, whereas cuffs around larger vessels filled more slowly. No cuffs were visible around vessels smaller than 0.1 mm diam. After 45 min cuffs had formed around 99% of all vessels larger than 0.5 mm diam but had formed around only 38% of veins and 91% of arteries of smaller diameter. We simulated the observed rate and pattern of cuff growth using electrical analog models. The filling pattern and model analyses suggest that liquid entered the interstitium from an air space site associated with arteries of approximately 0.1-1.0 mm diam, spread to adjacent sites, and eventually reached the lobe hilum. The estimated perivascular interstitial flow resistance decreased approximately 100-fold with cuff expansion.