During the past two decades, major investigative interest has been focused on the determinants of chronic renal disease and interventions to retard the inexorable progression to end-stage renal disease. Recent studies have provided a theoretic framework for anticipating that angiotensin-converting enzyme (ACE) inhibitors, and possibly calcium antagonists, may preferentially retard the progression of renal disease. Whereas the majority of available clinical trials have assessed the effects of ACE inhibitors in patients with insulin-dependent diabetes mellitus (IDDM), there are relatively few long-term studies that have evaluated the renal protective effects of ACE inhibitors and calcium antagonists in patients with nondiabetic renal disease. Although clinical trials have been initiated using both of these drug classes as monotherapy, theoretical considerations suggest that fixed-dose combinations of an ACE inhibitor and a calcium antagonist might be appealing as renal protective agents. Several lines of evidence suggest that the renal microcirculatory effects of coadministration of both agents should be complementary. Similarly, recent observations suggest that the two classes may act in a complementary manner to countervail pathogenetic mechanisms at the level of the mesangium. A recent study in type II diabetic patients demonstrated that combination therapy with an ACE inhibitor and a calcium antagonist induced the greatest reduction in proteinuria, and reduced the rate of decline in glomerular filtration rate (GFR) more than did either agent alone at the same level of blood pressure reduction. Based on such considerations, recent randomized prospective studies have been initiated to compare the renal protective effects of combination calcium antagonist-ACE inhibitor therapy versus monotherapy with agents of either of these two antihypertensive classes.