To study the metabolism of α1-antitrypsin in man, radioiodinated purified α1-antitrypsin of protease inhibitor type MM was injected intravenously into seven normal volunteer subjects of protease inhibitor type MM and plasma and urine radioactivity data were analysed. The purified glycoprotein inhibited trypsin and exhibited microheterogeneity characteristic of α1-antitrypsin on acid starch-gel electrophoresis. The intravascular mass was 116 + 16.1 mg/kg (mean ± SEM); extravascular/intravascular pool ratio was 1.07 ± 0.067; the fractional catabolic rate was 33.3 ± 1.37% of the intravascular pool/day; half-life was 4.6 ± 0.21 days; synthetic rate was 33.8 ± 6.3 mg day-1 kg-1. The data indicated that the serum concentration of α1-antitrypsin varies independently of its fractional catabolic rate and that it is catabolized in, or in close relationship to, the intravascular compartment. Plasma curves of protein-bound radioactivity were also defined after the intravenous administration of 131I-labeled desialylated α1-antitrypsin to two additional subjects. The fractional plasma disappearance rates were approximately 150 times as great as those for the intact protein. The rapid disappearance of 131I-labelled desialylated α1-antitrypsin from plasma coincided with an equally rapid uptake of radioactivity by the liver. The results are compatible with the existence of receptor sites for desialylated glycoproteins in the surface membrane of human hepatocytes and emphasize that the catabolism of α1-antitrypsin can be influenced by the structure of its carbohydrate moiety.