The objective is the understanding of hereditary factors affecting alpha sub 1-antitrypsin and leucocyte lysosomal proteases in individuals predisposed to emphysema. Using methods of protein purification and sequence analysis, genetic variants of alpha sub 1-antitrypsin will be characterized and tested for their ability to bind to and neutralize proteases. Any imbalance in the relative amounts of major and minor forms of the protein will be noted. The neutral and basic proteases in polymorphonuclear leucocyte lysosomes will be characterized in normal individuals and patients demonstrating early or familial emphysema with normal serum alpha sub 1-antitrypsin. The type and severity of obstructive lung disease will be determined in patients having variant protease or inhibitor molecules. The relationship of the genetic factor to the disease may then be inferred, and screening tests may be devised to identify susceptible individuals early in life.