In order to study the role of brain biogenicamines in the regulation of ACTH secretion under basal and stress conditions, we examined changes in plasma corticosterone and hypothalamic CRF levels in male and female rats following either the intraventricular injection of biogenic amines or drug-induced changes in brain amine content. Various amounts (from 1 to 250 µg) of norepinephrine (NE), dopamine (DA), serotonin, carbachol and γ-aminobutyric acid (GABA) were injected into the lateral ventricle of the brain of conditioned unanesthetized rats through chronically-implanted cannulae. All the substances except GABA elicited a significant increase in ACTH secretion at the higher doses used. The stimulatory effects of centrally administered amines were partly abolished by prior treatment with reserpine or with reserpine along with Nembutal. Brain amines were depleted by pretreatment with either reserpine or 6-hydroxydopa-mine. In spite of the persistence of marked depletion of hypothalamic NE content, the basal circadian rhythm as well as stress-induced changes in both plasma corticosterone and hypothalamic CRF levels were preserved in almost the normal fashion. In addition, more than two-fold increases of brain amine concentration by pretreatment with a MAO inhibitor affected neither basal circadian rhythm nor a stress-induced increase in the plasma corticosterone. These observations suggest strongly that brain amines are of relatively little importance in the central regulation of ACTH secretion in the rat.