A summary has been included at the end of each section, but the scope of the thesis may be reviewed by way of conclusion. Attention has chiefly been directed to a study of anatomical and physiological abnormalities in the peripheral arterial circulation. Methods of investigation were described in the first two sections. The pathological anatomy was studied by gross dissection of amputated limbs supplemented by histological and injection technique. Physiological disturbances were observed by performing exercise tolerance tests and by measuring circulation .times by the reactive hyperaemia and fluorescein methods. Particular attention was paid to the use of the Greenfield and Scarborough type of hand calorimeter and of plethysmographs for the upper and lower limbs. The majority of the observations have been made with these two instruments and the precautions necessary to obtain accurate readings were accordingly detailed. An electrical capacitance manometer designed for the direct recording of pressure in the peripheral arteries was described. The pathological anatomy of peripheral vascular disease in the lower limbs was investigated and the changes found in younger subjects with thromboangiitis obliterans and in older subjects with atherosclerosis were described. Thromboangiitis involved chiefly the small distal arteries of the extremity while atherosclerosis affected the larger more proximal arteries. In each disease the development of thromboses obstructing the arteries and spreading to occlude the origins of collateral vessels was responsible for the onset of ischaemic gangrene. The recamalisation of obstructed arteries was studied in detiaii, particulary with regard to the development and function on of the elastic-coated vessels seen penetrating the organised thrombus. The changes in blood flow and blood pressure resulting from these anatomical abnormalities were described. In diabetes mellitus of long standing it was shown not only that there was a premature atherosclerosis of the arteries in the limbs, but also that the smaller vessel were affected. Damage to the latter might, in many cases, be chiefly responsible for the development of symptoms of ischsaemia. The blood flow distal to a coarctation of the aorta was investigated and it was shown that the presence of this congenital abnormality did not reduce the maximal circulatory capacity of the limbs applied by the collateral arteries. Popliteal aneurysms of atherosclerotic origin were not associated with an unobstructed distal arterial pathway. Clotting within the aneurysm was a dangerous complication and the effect of such an aneurysm was to reduced the distal circulation. On the other hand, a pulsating syphilitic aneurysm on the axillary artery with the distal arteries unobstructed augmented the peripheral blood flow. This increase beyond the reç±uirements of the distal tissues led to the development of unilateral clubbing of the fingers. The blood flow distal to a coarctation of the aorta was investigated and it was shown that the prescence of this congenital abnormality did not reduce the maximal circulatory capacity of the limbs applied by the collateral arteries. The circulatory changes associated with clubbing were investigated in selected cases and it was shown that an increased peripheral circulation above the volume normally required by the tissues was essential for the development of clubbing. The excess blood was shunted through arteriovenous anastomoses situated in the finger and to a lesser degree in the toes and lobes of the ears. The central mechanisms that might give rise to this excessive peripheral blood flow were considered. Tn general they led either to an output of blood from the left ventricle greater in volume than the requirements of the tissues supplied by the systemic arterial circulation, or to an increase in blood volume. The grossest degrees of clubbing were seen when both factors together were operative. The circulatory, changes brought about by the infusion of noradrenaline into healthy subjects were described. Three cases of phaeochromocytoma were investigated particularly with regard to the associated abnormalities in the peripheral circulation. It was shown that persistent arterial hypertension was not due to the continuous release of noradrenaline into the circulation. The investigations have thus been mainly concerned with the study of arterial disease and 211 hypertension, the two major problems confronting medicine today. They have been directed largely towards the mechanism of the development of these diseases and thus throw little light on their underlying aetiology. No apology is, however, reouired for this fact for elucidation of the mechanism is the first logical step towards the investigation of the fundamental underlying cause.