Studies of ethchlorvynol (ECV)-induced pulmonary edema were undertaken for determination of the structural basis of increased microvascular permeability. Rats were administered an intravenous bolus dose of 15 mg/kg ECV and killed at time intervals between 5 minutes and 72 hours. Oyster glycogen and ferritin were used as permeability probes for identification of the sites of altered microvascular permeability. Edema fluid containing ferritin begins to accumulate in the alveolar interstitium 10 minutes after EVC . Thirty minutes after ECV, marked intersitial edema fluid is present containing both permeability probes. The absence of any appreciable transendothelial movement of either probe via vesicles and the presence of open endothelial junctions led the authors to propose the latter as the principal determinant of the increase in permeability. In addition to open endothelial junctions, prominent subendothelial blebs occur. These blebs develop in an otherwise intact endothelium and increase in frequency and size with time following their appearance at 10 minutes. Ferritin and glycogen progressively accumulate within the blebs. At 15 minutes the concentration of ferritin in blebs appears to equal that in plasma, whereas glycogen is absent or sparsely present in a few blebs. At 60 minutes both permeability probes have become concentrated in the blebs. The mechanism of formation of the blebs and concentration in them of the permeability probes cannot yet be specified. The lesion caused by ECV is completely reversible, so that by 72 hours after ECV there is complete resolution of interstitial edema, disappearance of the subendothelial blebs, and closure of endothelial junctions. A small amount of exudate remaining in the alveoli is cleared by 72 hours.