Atrial natriuretic peptide (ANP) or an Atriopeptin III analog (PL 058) stimulated cGMP formation in the membrane fraction of rat olfactory bulb, median eminence and paraventricular nucleus, in a dose-dependent manner. The effect of the Atriopeptin III analog was 20-40% greater than that of ANP. Bilateral adrenalectomy, with or without mineralo- or glucocorticoid-replacement, on ANP-stimulated cGMP formation was investigated in rat paraventricular nucleus. 11 days after bilateral adrenalectomy a reduced responsiveness to ANP- or PL 058-induced cGMP production was observed. This effect was prevented by deoxycorticosterone, but not by dexamethasone administration. Our results further support the presence of guanylate cyclase-coupled ANP receptors in brain localized target sites; and they provide evidence suggesting that guanylate cyclase-linked ANP binding sites in the PVN are susceptible to regulatory changes after adrenalectomy-induced activation of the hypothalamus-hypophyso-adrenocortical system.