It is evident from many histories that large dosage robbed of or modified in its toxic effect, and even in the opiate manifestations usual in subjects who have never been made tolerant, and small dosage being sufficient to re-awaken physical need for opiates are conditions which do exist and persist for indefinite periods. The resemblance between this continued tolerance and the conditions existing in diseases which confer immunity and having a generally accepted antitoxin mechanism is too close to be ignored. Evidence of a toxic substance in the body of a narcotic-addict is further presented by the similarity of the clinical pictures presented by these cases of acute opiate need and extremely severe cases of acute poisoning from materials such as the ptomains and some other poisons. Acute opiate need is clinically typical of intense suffering and prostration from the action of some powerful poison. Its symptoms cannot be due to opiate, for the reason that the administration of opiate relieves them, and relieves them exactly in ratio to the amount of opiate administered. They can be held at any given stage by gradation of the opiate dosage. Their manifestations, moreover, are exactly opposite to opiate effect. They are to my mind best explained as due to the action of some toxic substance, antidotal to opiate, prepared by the body for its protection in response to continued opiate presence in the body, as antitoxins are prepared for the neutralization of or opposition to the organic poisons of invading bacteria. The chemical or physical character or nature of such substance has not been yet determined. The presence of such a substance would explain the establishing of tolerance, the manifestations following opiate administration and the apparent definiteness of the amount of opiate needed. It would explain the results of under-dosage and the results of over-dosage, and the practical non-interference with function or general health when a dosage is maintained exactly sufficient in amount to neutralize the effect of some exactly antidotal body or substance.