A direct study of the isolated rat liver perfused with oxygenated blood containing amino acids and lysine-ε-C14 has yielded facts indicating that the liver synthesizes practically all the plasma fibrinogen, the albumin fraction, and probably more than 80 per cent of the plasma globulin fraction. The response of the isolated perfused liver in protein synthesis is qualitatively and quantitatively analogous to that of the intact animal, notably in (a) the ability to discriminate between natural L-lysine and D-lysine, (b) the per cent of isotopic amino acid converted to CO2, (c) the per cent utilized in liver and plasma protein synthesis. The results obtained with the perfused liver are compared and contrasted with those reported for tissue homogenates, minces, and slices.