The major aim of this research is to explore the relationships between plasma levels of chlorpromazine and its metabolites and prolactin, and discrete aspects of clinical response in schizophrenia. Prolactin is a pituitary hormone whose secretion is increased following dopaminergic blockade by neuroleptics; thus, plasma prolactin levels provide a measure of the functional activity of the neuroleptics. Radioimmunoassays of chlorpromazine and key metabolites will be established which should be markedly superior to existing gas chromatographic methods in terms of the rate at which samples can be assayed with no loss of reliability or sensitivity. These methods could eventually have widespread practical utility as they are feasible for the general hospital lab. Pilot studies of red cell and fat levels of chlorpromazine and metabolites will also be determined. Studies will be conducted to determine if blood levels or tissue levels of chlorpromazine or its metabolites, or plasma prolactin are correlated with clinical response. Among our aims are: 1) to determine if a single dose administration of chlorpromazine can predict steady state levels of drug or prolactin; 2) to determine if administration of anticholinergic or lithium along with chlorpromazine lowers plasma levels of drug or prolactin; 3) to establish bioequivalent doses of the neuroleptics in terms of prolactin response. This grant will also permit neuroendocrine studies of patients with the major mental illnesses so that the state of pituitary dopamine receptors and other aspects of hypothalamic-pituitary bioamine activity can be assessed. For example, the change in prolactin levels in unmedicated schizophrenics following administration of apomorphine, dopamine infusions, alpha-methylparatyrosine, or tryptophane will be studied and in some instances compared with that of volunteers.