OBJECTIVE: Diabetic nephropathy (DN) is a leading cause of kidney disease in the US. At least four factors influence whether people with diabetes will develop DN: (1) hypertension, (2) hyperglycemia, (3) dietary protein intake, and (4) intrarenal hemodynamics. The angiotensin-converting enzyme (ACE) inhibitors are known to affect blood pressure (BP) and intrarenal hemodynamics; thus, they may prevent the onset of DN or slow the decline in renal function once DN has been diagnosed. DATA SOURCES: English-language, controlled, and crossover studies published between 1973 and 1991 and indexed in MEDLINE under the headings diabetic nephropathies and angiotensin-converting enzyme inhibitors. MAIN OUTCOME MEASURES: The primary outcome indicators of interest were the effects of the ACE inhibitors captopril, enalapril, and lisinopril on BP control and urinary albumin excretion rate. CONCLUSIONS: ACE inhibitors delay the onset and slow the progression of DN in people with diabetes independent of BP effects. They also slow the progression of DN in people with diabetes who have poorly controlled hyperglycemia. The proper dose and time at which to initiate ACE inhibitor therapy to prevent the appearance of DN is not known. It is also not known how long the beneficial effects of ACE-inhibitor therapy persists as only two studies have followed patients for more than one year. Finally, large, long-term, controlled clinical trials are needed before ACE inhibitors can be considered for prophylactic use to prevent the onset and/or progression of DN.