Alpha-1-proteinase inhibitor (human) (A1PI) has now been prepared as a lyophilized concentrate and has been tested clinically in humans with A1PI deficiency (also called alpha-1-antitrypsin deficiency). The protein was purified from plasma (Cohn fraction IV-1) by precipitation and ion-exchange chromatography. The resulting product behaves almost indentically to the A1PI in plasma, showing that the process is gentle and nondenaturing. In order to lower the risk of transmission of disease, the product has been heat-treated. Although this resulted in some aggregation of protein, no new antigenic sites were created. Biologic, immunologic, and physiologic studies have shown that the protein behaves normally.