1. Extravascular albumin in carcass, skin and gut of rats was extracted and the albumin content estimated by several methods. Assay by electrophoresis on acrylamide gel, by immunodiffusion and by radioimmunoassay were in essential agreement. The method used previously, precipitation with antibody followed by alcohol-TCA extraction, underestimates the amount of albumin in tissue extracts, because extraction from the antibody precipitate is not complete. This method is valid, however, for specific activity determination.
2. Normal rats contain from 500 to 650 mg of albumin per 100 g body weight. Of this, 20–25% is in the circulation, 35–40% in the carcass (mainly but not exclusively muscle), 20–25% in skin and 10% in gut.
3. The extracellular water of muscle, carcass, skin and gut was estimated from the distribution of mannitol and sulphate. With the exception of gut, both methods agreed closely. Extracellular, extravascular water constitutes about 23% of the body weight of 150–200 g rats. The extracellular water in muscle is about 20% and in skin, 40%. In gut the extracellular water cannot be estimated reliably by these compounds.
4. Muscle contains about 3·5 mg/g of extravascular albumin; skin and gut, 7–8 mg/g. The concentration of extravascular albumin in extracellular water of muscle and skin is 1620 mg/ml, or 5060% of the concentration in plasma. In the small intestine the concentration of albumin is higher, possibly similar to that in plasma.
5. In rats with severe aminonucleoside nephrosis, body albumin was depleted to 100–200 mg/100 g. Of this, 15–25% was in plasma, 50% in carcass, and about 15% in skin. Ascitic fluid contained only a few mg of albumin.
6. The specific activity of extravascular albumin of tissues was followed after intravascular injection of 125I- or 131I-labelled albumin. The specific activity of carcass albumin increases rapidly, becoming equal to that in plasma after less than 2 days. The specific activity of albumin in skin increases much more slowly and becomes equal to that of plasma after 4 days. Labelling of albumin of gut is even slower. The specific activities in tissue never exceed that in plasma.
7. In severely nephrotic rats, specific activities in carcass and skin become equal to that in plasma within 2–3 days and remain equal thereafter. Specific activity of albumin in ascitic fluid increases to reach values as much as sixteen-fold those in plasma.
8. The extravascular pool, as calculated by multicompartmental analysis from the slopes and intercepts of the plasma curve, is about equal to that in plasma and in severely nephrotic rats is less than that in plasma. Discrepancies between calculated and observed extravascular albumin masses is by a factor of 3 in normal rats and 10 or more in severely nephrotic rats.
9. Specific activity of extravascular albumin as calculated from multicompartmental analysis is 1·5 times that in plasma in normal rats and at least six times that in plasma in severely nephrotic rats. Actually, the specific activities in extravascular and vascular albumin ultimately become and remain equal.
10. It is concluded that the multicompartmental model of vascular pool exchange with one or two extravascular pools is not valid for rats and probably not for other animal species.