ANP harbors truly remarkable properties in having demonstrable interactions at several key loci of the systems that control blood pressure and extracellular fluid volume. The discovery of ANP by deBold and colleagues succeeded in bringing together neighboring scientists (that is, nephrologists, endocrinologists, cardiologists, and vascularologists), whose research efforts do not often coalesce, in attempts to define the pharmacology and physiology of this peptide. Although we have witnessed a tremendous explosion of interest and work over the past 6 years, several areas of research need to be pursued to obtain these goals. ANP appears to lower blood pressure by reducing either afterload or preload, with the sympathetic state of the individual having an important modulating effect. ANP causes an increased renal secretion of electrolytes, although there is yet to be uniform agreement on the underlying mechanism(s). The depressor and natriuretic effects of ANP act in harmony with an inhibitory effect on the release of aldosterone, renin, and vasopressin. Although this intriguing pharmacologic foundation of ANP has been laid, the physiologic role or importance is still in question. Nonetheless, as we gain further insight into the pharmacology, we stand to advance our knowledge of, and hopefully develop more useful regimens for, cardiovascular and renal pathologic states. As would be expected of an agent that may interact at multiple regulatory sites for control of hemodynamics and fluid volume, differences will most likely exist among species in the pharmacology of ANP, not only as a function of structure-activity relationships but also as a consequence of phylogenic differences in the integration of cardiovascular control.