AbstractThe neurobiology of drug addiction is being clarified. Research is revealing the anatomic pathways of primary drug reinforcement (reward) in the brain and the molecular architecture of the receptors on which addictive drugs act All addictive drugs mimic (or occasionally block) the actions of some neurotransmitter; in the case of heroin or methadone an endogenous opioid, probablyβ-endorphin. The ground work is being laid for understanding Dole and Nyswander's“metabolic disease”concept as a concrete neurochemical abnormality of the endogenous opioid system. Thus, a stronger basis is developing for regarding methadone maintenance as a means of replacing a neurohormonal deficiency. Three practical conclusions that can be drawn from this model are: (1) methadone dosage must be adequate (never less than 50–80 mg); (2) it should be more widely accepted that some patients may require lifelong methadone maintenance; and (3) longer-acting, better stabilizing methadone congeners, such as LAAM and its metabolites, should be brought into general use.