Idiopathic membranoproliferative glomerulonephritis (MPGN) has a poor prognosis, with 90% of patients requiring dialysis treatment after 20 years regardless of therapy. Up to 34% of patients may die due to thrombotic complications or sepsis. This study investigates the influence of aspirin plus dipyridamole on proteinuria and renal function in nephrotic MPGN patients with moderately reduced glomerular filtration rate. Eighteen patients with biopsy-proven MPGN (15 type I, 3 type II) and nephrotic syndrome were randomly assigned to receive protein restriction, antihypertensive therapy (control group) or in addition aspirin and dipyridamole (treatment group). Patients were prospectively followed for a mean of 36 months. Serum creatinine remained unchanged after 36 months compared to baseline in both groups. In the treatment group proteinuria was reduced from 8.3 +/- 1.4 to 1.6 +/- 0.7 g/day (P < 0.05). In control patients proteinuria decreased from 7.1 +/- 1.6 to 4.3 +/- 1.1 g/day. After 36 months proteinuria was significantly lower in the treatment group compared to control (P < 0.02 Mann-Whitney rank sum test). In conclusion, aspirin plus dipyridamole may be of value in reversing nephrotic syndrome and associated risks in patients with MPGN and moderately reduced renal function.