Clinical studies evaluating the benefits of angiotensin-converting-enzyme (ACE) inhibitor therapy in patients likely to develop renal disease are reviewed. Patients with diabetes or hypertension are at increased risk for development of renal disease. In patients with diabetic nephropathy, captopril therapy was associated with a 50% reduction in the risk of death, dialysis, and transplantation and a significantly smaller increase in serum creatinine compared with placebo. Therapy with enalapril or lisinopril has been shown to limit the progression of renal disease in normoalbuminuric patients with diabetes. Long-term therapy with enalapril (up to seven years) has demonstrated the ability to preserve renal function in patients with diabetes and microalbuminuria. Over 4.5 years, patients with diabetes and at least one other cardiovascular risk factor had significant reductions in the risk of overt nephropathy with ramipril therapy compared with placebo. In addition, ramipril is associated with preservation of renal function in patients with nondiabetic nephropathy. Evidence suggesting a dissociation of the renal hemodynamic and antiproteinuric effects of ACE inhibition is presented. These positive effects of ACE inhibition cannot be explained by reductions in blood pressure alone. ACE inhibitors have renoprotective properties beyond systemic blood pressure reduction.