1. Human α1-antitrypsin was isolated with preserved microheterogeneity from subjects of Pi types M, S and MMalton. The M-protein was partially (20%) and completely desialylated. The proteins were labelled with either 125I or 131I.
2. The disappearance rate of these α1-antitrypsins was studied after simultaneous injection of the two types of labelled protein into Pi M subjects. The fractional catabolic rates of S- and MMalton-protein were 0.36 and 0.34 day−1 respectively compared with 0.28 day−1 for M-protein. The ratio of extravascular to plasma pools was 1.4 for S-protein and 1.6 for MMalton-protein. The 20% desialylated M-protein showed an increase of about 100% in its fractional catabolic rate. The disappearance rate of completely desialylated α1-antitrypsin was extremely rapid.
3. The slightly higher fractional catabolic rate of S- than of M-protein can only partly explain the 40% lower plasma concentration in subjects of Pi type S. Similarly the slight increase in catabolic rate of Pi MMalton-protein is too small to explain why the α1-antitrypsin content of the blood in Pi MMalton subjects is only 15% of that normally found. A low hepatic secretion seems to be the major cause of the low α1-antitrypsin concentration found in subjects of types Pi S and MMalton, as in Pi type Z.