The large scale fractionation of the pro teins of blood plasma was direct1y a product of the needs of military medicine in the United States during the war. Fundamentally, however, this development rests on a long series of advances in protein chemistry which have occurred over the last forty years in many laboratories, notably in England, Scandinavia, and the United States. The methods used for the fractionation of proteins depend on the laws governing the solubility of these substances. Our understanding of these laws has been derived, not only from the work of the protein and amino acid chemisis themselves, but also from other fundamental studies in the field of pure physical chemistry. All the advances of the last quarter century have been profoundly influenced by two fundamental studies, both published in 1923: the interionic attraction theory of DEBYE and HUCKEL (41) and the convincing demonstration by BJERRUM (11) that amino acids and peptides and, therefore, proteins also exist as dipolar ions in the neutral state. The theory of DEBYE and HUCKEL, as originally given, provided a basis for calculating the thermodynamic activities and hence the solubilities of electrolytes, as a function of ionic strength, dielectric constant, and temperature. The subsequent extensions of the theory by SCATCHARD and KIRKWOOD (126) and by KIRKWOOD (87) gave the basis for the treatment of dipolar ions along the same lines. Between 1930 and 1940 a large body of experimental evidence was obtained concerning the solubilities of amino acids, polypeptides, and related compounds in relation to their structure. This great body of empirical material could then be evaluated in relation to the theoretical treatments already indicated above, with the additional aid of some empirical generalizations that emerged from the data [for a summary of the work in this field, see the monograph of COHN and EDSALL (35)].