The renin-angiotensin-aldosterone system has an important role in the progression of both diabetic and non-diabetic nephropathy. COOPERATE was set up to determine whether dual blockade of angiotensin-converting-enzyme (ACE) and the AT-1 receptor was more efficacious than either ACE inhibition or AT-1 antagonism alone in non-diabetic renal disease. The combined primary end point was of time to doubling of serum creatinine concentration or end stage renal disease. By year 3, 10 of 85 (11%) of the combination patients had reached the primary end point. This was significantly less than the 20 of 86 (23%) and 20 of 85 (23%) in the losartan and trandolapril groups, respectively. Combination treatment should be considered in nondiabetic renal disease especially if the disease is progressing with ACE treatment alone.