The recently discovered cardiac peptides, called atrial natriuretic factors (ANF), act peripherally as hormones which control fluid and electrolyte homeostasis. Their renal, adrenal and vascular effects are complemented by central nervous system (CNS) actions to inhibit vasopressin secretion, salt preference, and water intake, and to inhibit the CNS component of the hypothalamo-pituitary-adrenal axis. These central actions of ANF are thought to mirror physiological roles played by endogenous, neuronally derived ANF within the brain. ANF immunoreactivity and binding sites in the anterior pituitary gland and median eminence suggest, as well, neuroendocrine actions of the peptide. We have failed to observe direct pituitary effects of ANF on basal or stimulated pituitary hormone secretion; however, specific hypothalamic actions have been discovered. ANF infusions (IV or cerebroventricular) inhibit luteinizing hormone (LH) secretion via, at least in part, an opioid mechanism since naloxone pretreatment blocks the effect. Additionally ANF inhibits catecholamine stimulation of the release of LH-releasing factor in the median eminence. Direct effects of ANF on tuberoinfundibular dopamine neurons are suggested by the observation that the prolactin-inhibiting action of ANF is prevented by domperidone treatment and is absent following alpha methyl-p-tyrosine inhibition of tyrosine hydroxylase activity. These recent results imply neuromodulatory actions of ANF within the CNS that are expressed via interaction with brain peptide and catecholamine systems.