Would it not appear that _powerful doses rather produce a local than a general effect_? Experience seems to prove in this respect, that the effect of an internal application is similar to that of an external impression; if violent, it affects the part only to which it is applied, as pinching does that of the skin, whereas titillation, which may be said to differ only from the former in degree, acts upon the whole system, and occasions itching and laughter, and if long continued, weakness, sickness, vomiting, and convulsions; in like manner _Digitalis_, if given in large doses, acts immediately upon the stomach or bowels, becoming emetic and cathartic, but in smaller proportions it produces a GENERAL effect, increasing all the excretions, especially that of urine; so, again, large doses of the _Mercurial Pill_ act upon the bowels, and are eliminated from the body, whereas the same remedy in small doses affects the system generally, and excites a universal influence. I am well satisfied that the regulation of the dose of a medicine is even more important than it is usually supposed to be. _Substances perfectly inert and useless in one dose may prove in another active and valuable._ Hence may be explained the great efficacy of many mineral waters, whilst the ingredients which impart activity to them are found comparatively inert, when they become the elements of an artificial combination; and hence probably the failure of many _alterative_ medicines, when no other rational cause can be assigned for it. We need not seek far for an example of the very different and opposite effects which the same substance can produce in different doses; the operation of _Common Salt_ is familiar to us all; Sir John Pringle has shewn that in quantities such as we usually take with our food, its action is highly septic, softening and resolving all meat to which it is applied, whereas in large quantities it usually preserves such substances from putrefaction, and therefore, when so taken, instead of promoting, destroys digestion. It is moreover probable that medicinal, like nutritive substances, are more readily absorbed into the circulating system when presented in small quantities, than when applied in more considerable proportions. It is upon this principle that a large quantity of food, taken seldom, does not fatten so much as smaller quantities at shorter intervals, as is exemplified in the universal good condition of cooks and their attendants. It is not pressing the principle of analogy too far to suppose that the action of _alteratives_, which require to be absorbed, may be more effectually answered by similar management; that is, _by exhibiting small doses at short intervals_.