Substitution therapy with human immunoglobulin preparations is well established in disorders of primary or secondary deficiencies of humoral immunity. However, modifications of the immunoglobulins are required to achieve tolerance for the preferred intravenous route of administration. Several procedures are employed by different commercial suppliers of immunoglobulins, and from the literature it appears that various important biologic functions, e.g., opsonic activity, complement fixation, and Fc‐receptor function, are subject to alterations during the preparation. The best preservation of such activity, when assessed in vitro, is obtained with polyethylene glycol precipitation or DEAE‐Sephadex fractionation, whereas enzymatic or chemical treatment can potentially reduce the biologic activity. It is recommended that immunoglobulin preparations be evaluated in vitro for intact biologic function before being given to immunodeficient patients.