In rabbits exposed to 100% O2 at 1 ATA from 48 to 72 hr, we measured the accumulation of intravenously injected 125I-bovine albumin, [57Co]cyanocobalamin, and 51Cr-erythrocytes in the intestine, skeletal muscle, heart, and lungs. From these data, we calculated the extravascular albumin and cyanocobalamin spaces (EVAS, EVECS) and the partition of water among vascular, interstitial, and cellular compartments in these organs. All variables remained at their base-line levels at 48 h in O2. At 64-66 h, the lung EVECS remained unchanged, but its EVAS increased by 210%. This change occurred after the previously documented increase of the alveolar epithelial permeability to solute and of the pulmonary conductance to water but before the appearance of pulmonary edema and arterial hypoxemia. The only change in the systemic circulation was a 17% increase of the heart EVAS. The increased heart and lung EVAS values, in the absence of any fluid volume shifts, are consistent with damage to the tissue polysaccharides of these organs by the toxic O2 species.