Secondary amyloidosis (AA amyloidosis) is a well known cause of nephrotic syndrome and renal failure. Several studies in patients with nephrotic syndrome have suggested a beneficial effect of angiotensin-converting enzyme inhibitors (ACEI). Angiotensin 11 (ATII) receptor antagonists effect on the long term is not known. In this study, we intended to study the effect of losartan, as an ATII receptor antagonist, on proteinuria and renal functions in patients with normotensive secondary amyloidosis. In total 44 patients with biopsy proven AA amyloidosis associated with nephrotic proteinuria were included. The first group of patients (n=22) was treated with losartan 50 mg/day. The second group of patients (n=22) did not receive any specific antiproteinuric treatment. Urinary protein loss was effectively lowered by losartan from 4.38+/-1.0 to 2.8+/-0.61 g/day (p<0.0001), whereas the control group showed a slight fall in proteinuria as 4.21+/-1.06 to 4.12+/-1.07 g/day (p=0.176). Hypoalbuminemia improved significantly from 2.52+/-0.69 to 2.78+/-0.46 g/dl (p=0.004), in the losartan group, whereas serum albumin had fallen in the control group from 2.44+/-0.57 to 2.27+/-0.41 (p=0.041). Serum creatinine increased in the control group from 1.52+/-0.42 to 2.39+/-0.51 mg/dl (p<0.0001), and in the losartan group from 1.59+/-0.50 to 1.84+/-0.6 mg/dl (p<0.001), after 24 months of treatment. The ATII receptor blocker losartan is effective in protecting against the progression of nephropathy due to AA amyloidosis. Symptomatic treatment of proteinuria with losartan is therefore to be considered, especially with severe proteinuria even in normotensive patients.