Atrial natriuretic factors (ANFs), produced in myocytes of mammalian atria, exert potent natriuretic and diuretic actions in the kidney as well as a variety of other actions coordinated to normalize extracellular fluid volume. Recently, ANF-like immunoreactivity has been detected in the hypothalamus of the rat, and central administration of ANF has been shown to block dehydration-induced water intake. We describe here the ability of 0.2 and 2.0 nmol atriopeptin III to inhibit saline intake when infused into the third ventricle of conscious, salt-depleted rats; an effect that was dose-related and long-lasting (24 h). These studies provide further evidence for a central nervous system action of ANF, which, together with its established renal and adrenal actions, might be an important feature of the coordinated physiological control of fluid volume.