Severe congenital deficiency for alpha1-antitrypsin is associated with the early onset of emphysema, usually by the third decade of life. One approach to correct this deficiency is though replacement with alpha1-antitrypsin (referred to as alpha1-proteinase (A1Pi) inhibitor in its purified form). An intravenous preparation of A1Pi concentrate was produced from human plasma by Cutter Biological, a division of Miles, Inc., Berkeley, California. This preparation had been evaluated in a clinical study for its safety and biochemical efficacy. Based on the augmentation of its levels in the lung upon intravenous administration, the A1Pi preparation was licensed by the Food and Drug Administration for replacement therapy to treat individuals with severe congenital deficiency and impaired lung function. When the registry began in 1988, clinical efficacy was plausible, but unproven and there was no data base for estimating the degree of clinical benefit, if any.