Abstract: Purification of &agr;-1 proteinase inhibitor (&agr;-1 PI) from aqueous solutions, such as human plasma, is accomplished by precipitation of contaminating proteins from the aqueous solution, followed by dilution of the solution to adjust its conductivity, and passing of the solution through an anion exchange resin. The conductivity of the solution is adjusted so that the &agr;-1 PI binds to the anion exchange resin, while other contaminating proteins and solvent pass through the resin. Further purification may be accomplished by cation chromatography, which takes advantage of the fact that &agr;-1 PI does not bind to the cation column under certain conditions. Some embodiments of the invention also include virus removal and/or inactivation by methods such as nanofiltration and such as contact with a non-ionic detergent. The methods of the present invention result in greater yield, purity, and pathogenic clearance of plasma fractions than known methods.