To study the accumulation and distribution of edema fluid and the associated changes in alveolar microarchitecture, edema was induced in excised rabbit lungs perfused with 6% albumin solution. The lungs, including the edema fluid, were then fixed by vascular perfusion with glutaraldehyde, osmium tetroxide, and uranyl acetate. Tissue samples were analyzed by light microscopy and transmission and scanning electron microscopy. We found (1) fixation was successful in that the albumin in the edema fluid formed coherent webs indicating the location and arrangement of the extravascular fluid accumulations; (2) regardless of the filtration pressure (about 29 mm Hg in one set of experiments and about 14 mm Hg in the other), an apical to basal gradient of fluid accumulation was found. This gradient was absent in lungs held in the inverse position, suggesting that the regional distribution of pulmonary edema is not simply gravity dependent. At the same lung height, there was a remarkable inhomogeneity of interstitial and alveolar edema. (3) Both the inhomogeneous distribution of fluid and the resulting changes in surface tension affected the entire alveolar architecture. (4) Within interstitial and alveolar spaces, there were striking inequalities in the density of the proteinaceous fluid pools that suggest local differences in the sieving properties of the barriers, that is, in the reflection coefficients for albumin. In conclusion, our findings suggest that the formation of pulmonary edema cannot be explained solely by uniform membrane models for fluid exchange.