The declining mortality due to coronary artery disease and stroke has been attributed in part to improved effectiveness and application of antihypertensive therapy, and successful identification and treatment of the population at risk. In striking contrast, end-stage renal disease (ESRD) attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Taken together, patients with diabetic nephropathy and those with hypertensive renal disease account for the majority of new cases annually. The reasons for the striking dissociation between the success with coronary artery disease and stroke on the one hand and the inability to lessen the incidence of ESRD remain to be clarified. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies suggest that antihypertensive treatment can prevent or retard development of progressive renal failure. No data are readily available on repeated measurement of glomerular filtration rate during prolonged treatment of mild hypertension in patients with normal or near-normal renal function. Although the importance of blood pressure control is implicit, a theoretical framework based on data derived from experimental animals suggests that angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists may exert specific renoprotective effects beyond those achieved by blood pressure reduction per se. The results of two recent long-term prospective studies support such a formulation.(ABSTRACT TRUNCATED AT 250 WORDS)