ANF immunoreactivity is present in specific, discrete brain nuclear groups; distinct, ANF-containing axonal projections have been mapped. The major concentration of ANF neurons resides along the walls of the third ventricle, in the anteroventral periventricular region. These cells project to neuroendocrine centers in the septum, medial preoptic area, paraventricular nuclei, and median eminence and to the periventricular thalamic nucleus. A second group of neurons project from the lateral hypothalamic area at least partly to the spinal cord. The third major group of ANF neurons projects from the region of the visceral centers in the pons and brain stem to the mesencephalic interpeduncular nucleus and the hypothalamus. Brain ANF is stored and released as the 24- and 25-amino-acid form, in contrast to plasma, where the 28-amino-acid form predominates, and the atria, where the larger prohormone is the stored form. The control of release of brain ANF appears to differ from that from the heart, as demonstrated during dehydration studies in the rat. CNS effects of ANF are predicted by the presence of specific ANF-binding sites and by the ability of iontophoretically applied ANF to alter single neuron excitability in a dose-related fashion. The major actions of ANF within the brain are well coordinated with its actions in the periphery and seem appropriate to its function as a controller of fluid volume and electrolyte composition. Thus, ANF's ability to oppose the action of vasopressin in the kidney is matched centrally by its potent inhibitory effect on vasopressin release.(ABSTRACT TRUNCATED AT 250 WORDS)