A broad program of a series of studies in five major areas of clinical psychopharmacology. Cholinergic mechanisms in clinical states will embrace treatment approaches to tardive dyskinesia, mechanisms in manic-depressive disorder and schizophrenia, and appropriate neurochemical studies. Neuroendocrine approaches to psychiatric treatment will embrace human pharmacologic studies of melatonin and its possible use in psychiatry. Clinical evaluation of new drugs will choose selected drugs for schizophrenia, such as baclofen or clozapine, or for depression. New leads to be followed will include the development of a pharmacokinetic model of chlormethiazone to allow its better use in the treatment of alcohol withdrawal, or the presynaptic receptor effects of apomorphine in conjunction with antipsychotic drugs. Methods to be employed include systematic clinical observations of each of the disorders being treated as well as extensive laboratory studies to support the clinical observations. Drugs will be used not only as potential treatments for patients but as probes to understand better the mechanisms of some of the disorders in question.