1. 1. Persistent experimental as well as human hypertension is probably due, fundamentally, to the operation of humoral agents, but nervous mechanisms may be temporarily or permanently active in addition. 2. 2. The dynamic resemblances and differences between experimental and clinical forms of hypertension deserve further study by apparatus more suitable for recording pressures in animals, and the results require better integration with changes in heart rate. 3. 3. The concepts of “central,” “collective” and “effective peripheral” resistances are analyzed, and formulas for mathematical calculation of the latter are given. 4. 4. Calculations of peripheral effective resistance by several formulas show that it is increased in various forms of human hypertension. But the magnitude of the increase does not necessarily correspond to the degree to which mean blood pressure is elevated, suggesting that other mechanisms are also concerned. 5. 5. Old and new experiments are reviewed which demonstrate that an intensive narrowing of small vessels in the splanchnic area must occur in order to produce elevations of pressure equal to those found in hypertension. Evidence is lacking that constriction of limb vessels contributes essentially to the height of pressure in animals or in man. 6. 6. Organic lesions are not generally distributed widely enough to account for the increased effective resistance, and there are good grounds for questioning whether significant narrowing occurs in restricted areas during life. The view that functional contraction of arterioles and prearterioles occurs is plausible, but we must not be too dogmatic in assigning the increased resistance entirely to arteriolar regions of the arterial tree. Some of the resistance may occur in vessels larger than prearterioles. 7. 7. Diminished elasticity of the aorta and its immediate branches accentuates the elevation of systolic pressure and reduces the diastolic pressure. It accounts also for the large pulse pressure and the rapid diastolic decline of subclavian pulses in hypertension. The absence of a significant increase in diastolic pressure, far from denoting inconsequential involvement of peripheral vessels, is probably more often a sign of an extension of vascular changes to the larger vessels. It is questionable whether the division of cases of human hypertension into systolic and diastolic types serves any useful purpose. 8. 8. Although sclerosis of larger vessels produces such changes, the suspicion has existed that aortic distensibility is also decreased, even when no pathologic changes are demonstrable. The view that in such subjects the aortic distensibility is decreased beyond that common for corresponding ages is supported by considerations arising out of new experiments on circulation models, on the perfused dog's aorta in situ, and by simultaneous records of aortic pressures and diameters in living dogs. 9. 9. Studies of pulse velocity are not destined to supply practical proof of the involvement of larger vessels in man owing to the difficulty of measuring arterial distances with sufficient accuracy. 10. 10. The hypothesis is suggested that the agent or agents that are concerned in the production of experimental and human hypertension tend to act along the entire arterial tree, causing contraction of the muscular elements. In the smallest peripheral vessels this narrows the lumen and increases peripheral resistance; in the aorta and distributing branches it reduces capacity and extensibility. 11. 11. Physiologically, the action of the left ventricle is not impaired as a result of the greater work imposed upon it by severe hypertension. In animals the output tends to increase, the mechanical efficiency is increased, and the economy with which the mechanical energy is utilized to propel blood is decidedly increased. 12. 12. In order to do this the ventricle operates continually in the region of cardiac reserve, and if additional distention occurs, e.g., because of an added return of blood, as during exercise, it responds with decreased, rather than, as normally, with increased output. This explains the limited capacity for exercise and development of the “effort syndrome” on exertion. 13. 13. Recent experiments in which changes in coronary arterial inflow under natural aortic pressures were studied by differential pressure curves indicate (1) that coronary blood flow increases as the systolic pressure, and (2) that mechanical adaptations between peripheral coronary resistance and aortic pressure, rather than nervous reflexes or chemical actions, are chiefly concerned.