We evaluated the long-term effect of an intensive treatment of diabetic nephropathy (anti-hypertensive drugs, low protein diet, multiple insulin injections to achieve a good metabolic control) on glomerular filtration rate (GFR) and albumin excretion rate (AER). Fourteen type I diabetic patients (mean age 45 +/- 9.5 years, mean duration of diabetes 23.5 +/- 7.3 years, 8 males/6 females) with glomerular filtration rate < 70 ml/min-1/1.73 m2 and albumin excretion rate > 30 micrograms/min were treated intensively for 36 months. This intensive treatment consisted of multiple insulin injections, antihypertensive therapy with ACE inhibitors and a low-protein diet (0.8 g/kg body wt/day.) Renal function was evaluated as GFR and AER. HbA1c mean value decreased significantly from 8.7 +/- 0.8% to 6.5 +/- 0.5% (P < 0.0002). GFR rose from 58 +/- 12 ml/min-1/1.73 m2 to 84 +/- 11 ml/min-1/1.73 m2 (P < 0.0008). AER decreased from 208 micrograms/min (range: 73 to 500) to 63.8 micrograms/min (range 15 to 180; P < 0.05). Systolic and diastolic blood pressure decreased respectively from 144 +/- 26 mm Hg to 120 +/- 15 mm Hg and from 89 +/- 9 mm Hg to 75 +/- 8 mm Hg (P < 0.01). We obtained a rise of GFR and a reduction of proteinuria after three years of this treatment. We suggest that this intensive treatment in all patients with early stage diabetic nephropathy may be effective in slowing the progression to renal failure.