The effect of long-term, aggressive, antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin-dependent diabetic patients (mean age, 30 years). Renal function was assessed every 4 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and by albuminuria (radial immunodiffusion). During the median pretreatment period of 2.4 years (range, 1.9 to 5.5 years), the GFR decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 9.7-year (range, 2.8 to 10.4 year) period of antihypertensive treatment with metoprolol, hydralazine, and furosemide, the arterial blood pressure decreased from 143/96 mm Hg to 130/84 mm Hg and albuminuria decreased from 1,038 micrograms/min to 547 micrograms/min. The rate of decline in GFR decreased from 10.7 mL/min/yr (range, 5.3 to 17.5 mL/min/yr) before treatment to 2.5 mL/min/yr (range, 0.5 to 4.8 mL/min/yr) during treatment. The rate of decline in GFR is significantly smaller during the last 6 years compared with the first 3 years in patients who received long-term antihypertensive treatment (> or = 9 years). One patient died from acute myocardial infarction (GFR, 46 mL/min/1.73 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.