The hypothesis of a natriuretic factor-originally an intriguing possibility and now an experimentally documented reality-has occupied the minds of scientists for more than 30 years. It has attracted not only experts in salt and water metabolism but also those interested in hypertension, because of the well known link between sodium homeostasis and blood pressure regulation. There are at least two distinct types of natriuretic substances: one is an inhibitor of the Na+K+ATPase and has been proposed to contribute to a rise in blood pressure; the other, now isolated from atrial tissue, is vasodilatory, natriuretic, diuretic, and has been demonstrated to decrease blood pressure. Our knowledge of regulation and function of this ANP has increased rapidly since its detection. Its role in blood pressure regulation is now fairly well understood. As depicted in Fig. 1, both synthesis and release of ANP are induced by atrial and ventricular wall stretch. In hypertension, distension of the left atrium and ventricle may be of particular importance for ANP release. The endocrine function of myocardial cells is stimulated in response to wall stretch in the ventricle. ANP is synthesized and stored as a 126 amino acid prohormone. Enzymatic processing of this prohormone to the circulating forms ANP 1-98 and ANP 99-126 takes place within the myoendocrine cells. The biological effects of ANP 1-98 are as yet unknown. ANP 99-126 acts at multiple sites to reduce blood pressure. One may distinguish between acute and more chronic effects. The acute effects include shift of fluid to the extravascular compartment and vasorelaxation. This shift is indicated by the rapidly developing rise in haematocrit, which is observed in intact as well as in nephrectomized rats and therefore not due to diuresis alone. The reduction of blood volume in addition to an increase in venous capacitance may be responsible for the reduced cardiac output. The latter may cause a reflex activation of the sympathetic nervous system and an increase in peripheral resistance, thereby overriding the vasodilator effects of the peptide. ANP appears to have a 'de-pressor' effect rather than a direct vasodilator effect. A lowering of peripheral resistance in response to ANP is not observed in normotensives, but is readily seen in at least certain forms of hypertension associated with an increased vascular tone. This most likely explains the discrepancy in the haemodynamic responses to ANP in normotensives and hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)