It is now known that cardiac atria play an important role in blood pressure and volume regulation. Mechanical distension of the atria results in the release of a potent diuretic and natriuretic agent or agents termed the atrial natriuretic factor (ANF). Several structurally related forms of ANF exist in man and it is thought that these represent precursory forms of a single optimally active molecule and/or the presence of more than one form of active ANF. The chemical structure of ANF between different mammalian species is similar. ANF receptors have been identified in kidney, brain, vascular endothelial and smooth muscle cells, tracheal and bronchial smooth muscle and the adrenal glands of many mammalian species, including man. This would suggest that ANF influences blood pressure and volume homoeostasis by affecting any one of a number of biochemical or physiological mechanisms via different target tissues. ANF is now considered a potentially valuable therapeutic agent for the treatment of hypertension and congestive heart failure. Synthesis of potent receptor antagonists could be extremely useful in the treatment of various clinical situations which are produced or complicated by endogenously produced ANF, such as chronic orthostatic hypotension.