Defibrotide is an antithrombotic agent that is capable of increasing the synthesis and release of prostaglandin I2 from endothelial cells, and improving fibrinolysis. The aim of this study was to evaluate the effectiveness of defibrotide therapy in slowing down the rate of progression of immunoglobulin (Ig) A nephropathy in patients with impaired renal function at diagnosis. 20 such patients were randomised to receive either prednisolone for 6 months plus defibrotide for 2 years (group A) or a 6-month prednisolone course only (group B). No significant difference was found at baseline between the two groups with regard to renal function, daily protein excretion or renal histological lesions. After 24 months, patients in group A had a mean decrease in serum creatinine level of 14%, compared with a 9% increase observed in group B (p = 0.007). A 14% increase in creatinine clearance occurred in group A patients as opposed to a 12% decrease in group B (p = 0.003). Daily protein excretion was significantly reduced in group A relative to baseline (p = 0.02), while it did not change in group B. These results suggest that nonimmunological factors are important in the progression of IgA nephropathy and that drugs that improve renal haemodynamics can contribute to the maintenance of renal function.