In constructing the argument for the following study, I am beholden more especially to three facts, the knowledge of which came to me as the direct result of experimental tests. One may place confidence, therefore, in the procedure which I have based upon these premises, for at no point, I think, in the following argument will mere affirmation be found to have usurped the place of sound induction. Without anticipating further, then, let me specify as briefly as may be the nature of these facts. PREMISES OF ARGUMENT. _First Fact._--The amount of ether, chloroform, chloral hydrate, the bromides, strychnine, and many other remedies, required to produce physiological effects upon the cerebro-spinal mechanism may be reduced by first securing a ligature around the central portion of one or several of the limbs of an animal, so as to interrupt both the arterial and venous circulation. The proof and explanation of this may be thus presented: In the first place, it is well known that children and small animals are affected by much smaller quantities of anaesthetics and other medicinal substances than are required to produce equal effects in men and large animals. At first sight, there appears to exist a certain definite relation between the weight of the animal and the quantity of medicament required to produce physiological effects. On closer inquiry, however, we find behind this proposition the deeper truth that the real proportion is between the magnitude of the blood-mass and the amount of medicament. Thus, if we withdraw a considerable amount of blood from a large dog, we may be able to affect him by much smaller doses than those required under ordinary circumstances; and, among human beings, we find the anaemic much more susceptible to remedies than the full-blooded of equal weight. The degree of saturation of the blood-mass with the remedy is obviously, then, the principal thing; the greater the amount of blood, the more remedy--everything else being equal--we shall have to give in order to obtain definite results. If we wish to embody the proposition in a mathematical statement, we may do so in the following simple manner: Let a represent the total quantity of blood, _b_, the amount of remedy exhibited, and _x_ the magnitude of the physiological effect. We shall then have the simple formula, x = b / a. Again, if we withdraw a certain quantity of blood from the circulation by venesection, and call that amount _d_, we shall then have the formula x = b / (a-d).