With the recent introduction of high-dose intravenous immunoglobulin treatment the preparations have to fulfill more stringent requirements with respect to safety and efficacy. Intravenous tolerance may be achieved by mild fractionation methods in combination with the elimination of anticomplementary aggregates. In early preparations enzymatic digestion or chemical modification of all immunoglobulin molecules was applied. Modern methods try to eliminate the anticomplementary aggregates more specifically by, e.g., precipitation, adsorption or mild acid treatment. Viral safety necessitates an adequate plasma quality in combination with the fractionation method and stringent GMP measures. Full efficacy of a polyvalent immunoglobulin preparation can be achieved by the isolation of the complete antibody spectrum in a native state. The fractionation method has to take care of the wide isoelectric region of the antibody population. The treatment used to achieve intravenous tolerance shall not damage the specific physiological functions of the immunoglobulin molecules. An optimization of the yield guarantees the supply and helps to keep the costs on an acceptable level.