Abstract. Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m 2 . Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes (1,2). Antihypertensive treatment, especially ACE-I, has been shown to reduce albuminuria, to diminish loss of kidney function, and to improve survival in type I patients with DN (1-3). Studies of diabetic and nondiabetic kidney disease suggest the initial degree of reduction in albuminuria after blockade of the reninangiotensin system (RAS) predicts an attenuated rate of decline in GFR, as reviewed by Rossing (1). As a consequence, albuminuria may serve as a surrogate end point for monitoring treatment efficacy and prognosis in DN (4).A superior effect on BP and a tendency toward a more pronounced drop in urinary albumin excretion of dual blockade of the RAS compared with single blockade has been reported in type II patients with microalbuminuria (5). We have recently shown additional drop in albuminuria and diastolic BP when adding an angiotensin receptor blocker (ARB) to angiotensinconverting enzyme inhibitor (ACE-I) treatment in type l patients with albuminuria Ͼ1 g/24 h and BP Ͼ135/85 mmHg, despite conventional antihypertensive therapy including three different agents (6). However, this subgroup is highly selected; therefore, it may differ from the patients in general with DN, especially with regard to RAS activity and ...