1. Complexes of human trypsin and human granulocyte elastase with α1-anti-trypsin and α2-macroglobulin were isolated and injected intravenously into human volunteers.

2. The elimination of α2-macroglobulin complexes with trypsin and elastase followed single-exponential functions with half-lives of 9 and 12 min respectively. The complexes showed no tendency to dissociate.

3. Complexes of α1-anti-trypsin with trypsin persisted in the circulation much longer, with a half-life of 3·5 h; complexes of α1-anti-trypsin with elastase had an intermediate half-life of 1 h.

4. Dissociation was observed of α1-anti-trypsin complexes with transfer of trypsin and elastase to α2-macroglobulin.

5. Dialysable radioactivity appeared in the urine soon after the injection of α2-macroglobulin complexes, which suggested a breakdown of complexes by cells in the reticuloendothelial system. Radioactivity over the liver achieved maximum values within 30–40 min after the injection of α2-macroglobulin complexes but not until 50–70 min after the injection of α1-anti-trypsin complexes.

6. These results support the concept of a key position for α2-macroglobulin in the protective mechanisms against endogenous proteases.

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