Hypertension is, after all, a physiologic response on the part of the organism in order to maintain the circulation in equilibrium in the face of conditions which tend to produce vasoconstriction in large areas and, therefore tend to deprive these areas of blood. That there must be some substance in the blood stream which causes this constriction seems certain. What it is, is not at present known. Recently, Voegtlin and Macht[7] have isolated a crystalline substance from the blood of man and other mammals which they regard as a lipoid and closely related to cholesterin. This substance was recovered by them from the cortex of the adrenal gland. This becomes of added interest in the light of observations made by Gubar (quoted by Voegtlin and Macht). He noted "that the vasoconstricting properties of blood serum vary in different pathologic conditions, being increased in nephritis, for instance, and diminished in others." In some experiments made in the summer of 1913, we found there was no marked difference in the anaphylactic shock produced in half-grown rabbits by the injection of normal and uremic blood serum. As lipoids do not cause anaphylaxis, there should be no difference in the reaction of normal and uremic sera unless in one there was some form of protein not in the other. This does not seem to be the case. The presence of something in the circulation, therefore, produces constriction of vessels. This calls for more force in contraction on the part of the heart. This substance may be of lipoid nature. The continued presence of this hypothetical substance naturally would lead to hypertrophy of the heart. [7] Isolation of a New Vasoconstrictor Substance from the Blood and the Adrenal Cortex, Jour. Am. Med. Assn., 1913, lxi, 2136. What makes hypertension of significance is not the hypertension itself, but the fact that it is the expression of processes going on in the body which demand exhaustive investigation. To attach a blood pressure cuff to the arm, find the pressure, and diagnose hypertension is like putting a thermometer under the tongue, noting a rise in the mercury, and diagnosing fever. What causes the hypertension? Can the causes be removed? Those are the really vital questions after the symptom hypertension has been discovered. All states of hypertension are accompanied by more or less increase of pulse pressure. In other words the systolic pressure is always increased to greater degree than the diastolic pressure. In studies carried out in the wards and Pathological Laboratory of the Milwaukee County Hospital, Milwaukee, we found that in all of the cases of chronic high blood pressure with resulting high pulse pressure four correlated factors were found. If any one of these factors is present, the other three are found.