With the expression cloning of the subunits of the epithelial sodium channel, a new era has evolved in our basic understanding of the low-renin forms of human hypertension. The monogenic hypertensive syndromes manifest dysregulation of the epithelial sodium channel in the cortical collecting tubule. These rare syndromes provide a schema for organizing our thinking about the more common form(s) of low renin hypertension, and raise the possibility that dysregulation of sodium channel activity and consequent salt retention and volume expansion provide a basic pathophysiological mechanism for low-renin hypertension. What are needed are more specific agents to interrupt the mineralocorticoid response pathways, and clinically relevant approaches to measuring sodium channel activity at the level of the collecting tubule in the individual patient. The combined use of aldosterone antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists could have a beneficial effect on "progression" of renal disease associated with glomerular and interstitial fibrosis, especially if the effects of hyperkalemia on the heart and aldosterone secretion can be minimized.