In this stage the “withdrawal” symptoms and signs become more evident as results of opiate deprivation. They proceed through the mild discomfort and nervousness of the previous stage to the definite manifestations and constant unmistakable withdrawal phenomena to be described. The patient endures physical suffering and displays all the clinical evidence of it. There can be no question of will-power in this stage, nor of desire for narcotic drug for any other purpose than to escape physical suffering. Whether the patient was primarily an innocent and unconscious recipient of the drug, or of the class of the vicious and weak, he is now fundamentally a sick man, afflicted with a physical disease. Whether or not he ever experienced any euphoria or sensuous enjoyment, he now gets nothing of pleasure from narcotic administration. He gets, _simply_, relief from suffering. The opiate drug has become his _only_ immediate means of securing and maintaining a physical efficiency, a semblance of normality. No other drug will take its place. He can take tremendous doses without toxic effect. In this stage, if the drug is denied or withdrawn without competent handling, his suffering and incompetency is not, as in the previous stage, a matter of days but may persist for weeks or months after no narcotic has been administered. The general stages of addiction-disease development as above rather superficially outlined are not of course sharply marked in their transitions. They slowly merge one into the next and taken together constitute a gradual development from normal reaction to opiate to established addiction-disease. Most patients are in or nearing the stage of developed addiction when they are recognized or come for treatment. Developed addiction for narcotic drug means physical, bodily need for that drug; functional incompetency and suffering without that drug; comparative normality and efficiency only to be immediately secured and maintained by the continued use of that drug. This is the situation of the sufferer from addiction-disease until such time as the activity of his addiction-disease mechanism is arrested. * * * * * Before I attempt exposition of the mechanism which seems to me best to explain addiction-disease and offer a basis for its rational handling, I shall offer several observations bearing upon physical or body reaction in the state of addiction.