The greater solubility of uric acid in blood plasma was, by Garrod and Haig, attributed to the _alkalinity_ of the plasma. But it must be recalled that the earlier workers in this sphere judged of the alkalinity of the plasma by its reaction to _litmus_, a crude procedure as compared with the use of _phenol-phthalein_, and Frankel’s _electro-potential_ measurements. Working with these as criteria, it has been shown that blood is normally _alkaline_ in only a _minority_ of cases, and indeed, according to Flack and Hill, the plasma is in reality _neutral_. In the _urine_ uric acid and the urates are held in solution by the neutral _phosphates_. This because the decomposition of the urates into uric acid by the acid salts of the urine is inhibited by the di-sodium phosphate present therein. Its maintenance in solution is possibly also reinforced through the influence of other constituents in the urine, notably, the urinary pigments and sodium chloride. URIC ACID IN THE BLOOD As to the form in which uric acid circulates in the blood, Sir William Roberts believed that when dissolved in blood serum it was transformed into the relatively soluble sodium _quadriurate_. This authority held that in gout, either through deficient excretion or over-production, the quadriurate accumulates in the blood. Circulating therein, in a medium rich in sodium carbonate, it takes up an additional atom of the base, and is transmuted into the _biurate_, which is less soluble and less easily excreted by the kidneys; consequently, the biurate is hoarded up in the blood, at first in gelatinous, and later in an almost crystalline form, when its precipitation is imminent or actually ensues. This, moreover, was apt to occur at sites where the circulation was poor, the temperature low, and more particularly in regions in which the plasma contained a relatively high percentage of sodium chloride, _e.g._, synovial sheaths. But, unfortunately for the valency of this otherwise plausible theory, it was proved by Tunnicliffe, Rosenheim, and others, that _quadriurates_ do not exist as definite chemical compounds; in short, it is generally conceded that their existence should no longer be accepted. GUDZENT AND SCHADE’S THEORIES Gudzent was of opinion that uric acid can only exist in the blood as the _mono-sodium-urate_, of which there are two isomeric varieties, the easily soluble unstable _lactam_, and the stable relatively insoluble _lactim_ urate. It is the former, or lactam, variety that accumulates in the blood in gout and, according to Gudzent, it is the transmutation thereof into the lactim modification that determines the precipitation of urates in the tissues. The lactim urate is soluble only to the extent of 8·3 mg. per 100 cc. serum, whereas the lactam form is soluble up to 18 mg.