Pribam in 1871 (cited by Loeb)35 first suggested that calcium exists in blood in more than one form. However, Rona and Takahashi51,52 in 1911, by using compensatory dialysis, showed for the first time the existence of blood calcium in dialyzable and nondialyzable forms and suggested that the latter was bound to protein. They found 75% of the total calcium to be diffusible.Many papers 3,4,25-29,34-36,38,54,57,60,61were published since then and many ideas were expressed regarding the different forms in which calcium existed, but without definite conclusions until 1934 when McLean and Hastings 40-43 performed some classical experiments by using the "frog's-heart" technique. They found 40% to 50% of the total calcium as ionic and an insignificant amount of diffusible calcium as reversibly bound to citrate. The nondiffusible calcium was accounted for by the presence of calciumprotein complex. The ionization of calciumproteinate was determined by an equilibrium between calcium and protein which could be described as a first-degree approximation by the mass law equation :(Ca++) X (Prot=) _K_|q-2.S Ca Proteinate They did not find any evidence for a calcium-phosphorus complex in the fluids of the body in normals. The effect of tem¬ perature, pH, and magnesium on ionic calcium was found to be negligible. Ap¬ parently the calcium ion concentration was normally maintained within a relatively narrow range by a process of physiologic regulation in which the parathyroid glands played a prominent role. The calcium ion was of primary physiologic importance.The range of calcium ions in normals was 4.25 to 5.25 mg. per 100 ml. of serum.Increased amounts indicated hyperfunctioning parathyroids, and the decreased levels indicated hypoparathyroidism or hyperphosphatemia of uremia. The calcium ion concentration of plasma at any time was the resultant of an equilibrium between the total amounts of calcium and protein pres¬ ent in the plasma. According to Hopkins and co-work¬ ers,32'33 ultrafiltrable calcium (diffusible calcium) normally ranged between 65% and 75% of the total, if the pH of the ultrafiltrate ranged between 7.3 and 7.7. They controlled the serum pH by saturating it with 5% CO2 in O2 prior to ultrafiltration. This information renewed interest in this problem.The purpose of this paper is to review older work and to present our data on :(a) the effect of pH and CO2 on ultra¬ filtrable calcium; (b) the changes occurring in respiratory acidosis and alkalosis; (c) the base binding property of different se¬ rum proteins with respect to calcium; and (d) the determination of ultrafiltrable cal¬ cium in some clinical disorders.Effect of pH and C02 on Ultrafiltrable Calcium Only a few earlier workers controlled the pH of serum during ultrafiltration. In 1921 von Meysenbug and co-workers 60 controlled the pH by saturating serum with 6% CO2. They found the ultrafiltrable calcium in healthy human beings to range between 60% and 70% of the total, and this was nearly the same in tetany. By the same method for controlling pH of s...