In pulmonary edema, fluid accumulates first in the interstitium, then in the alveoli. However, the relative amounts of interstitial fluid around arteries and veins of different sizes are unknown; in addition, the effects of fixation on the light microscopic quantitation of edema are unclear. To answer these questions, we induced permeability pulmonary edema in seven anesthetized dogs with 27 mg/kg of alpha-naphthylthiourea. Pulmonary artery and wedge pressures were measured. After moderately severe edema, diagnosed by chest x-ray and falling arterial pO2, lobes were fixed by airways instillation or vascular perfusion with glutaraldehyde and formaldehyde or were frozen with liquid nitrogen. With light microscopy, the edema surrounding arteries and veins of different sizes was measured using a computer equipped with a digitizing tablet and expressed as the edema ratio = area of perivascular edema/area of vessel, or as an absolute area of edema. Alveolar edema was graded semiquantitatively, and wet weight to dry weight ratios were calculated. Two control dogs were also studied. During the induction of edema, pulmonary artery and wedge pressures did not change significantly. Mean wet weight to dry weight ratios were 9.3 +/- 1.1. We found that the edema ratio was greater (p less than 0.01) for arteries (2.75, n = 1305) than for veins (1.40, n = 900). The edema ratio was greater for vessels more than 400 micron than less than 400 micron (p less than 0.01) and greater in the instillation- and perfusion-fixed lobes than in the frozen lobes (p less than 0.01). Similar results were obtained for the absolute areas of periarterial and perivenous edema. Less alveolar edema was seen in the lobes fixed by instillation (p less than 0.01). We conclude that, in permeability edema induced by alpha-naphthylthiourea, the fluid accumulates preferentially around arteries compared with veins and around larger compared with smaller vessels. Airways instillation and vascular perfusion fixation appeared to increase interstitial fluid cuffs compared to freezing.