The concentration of atrial natriuretic peptides (ANF) was measured radioimmunologically in 18 selected microdissected brain areas of rats with inherited diabetes insipidus (Brattleboro rats) and their control rats (Long-Evans rats). In 7 brain areas known to be involved in the regulation of fluid homeostasis or blood pressure (subfornical organ, organum vasculosum lamina terminalis, periventricular preoptic nucleus, perifornical nucleus, nucleus of the solitary tract, tegmentum pontis, arcuate nucleus) ANF concentration was significantly changed. After restoration of antidiuresis with the V2 receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) ANF levels of Brattleboro rats adapted at least partly to those of the control rats in all brain areas except the subfornical organ. Furthermore, ANF was then significantly changed in the supraoptic and paraventricular nuclei of DDAVP-treated diabetes insipidus rats. These data show that the central ANF system is sensitive for changes in electrolyte and fluid homeostasis.