The von Willebrand factor (vWF) has been used as a marker of endothelial dysfunction in several diseases. We measured plasma vWF in patients with immunoglobulin A nephropathy (IgAN). In a group of 10 IgAN patients with normal renal function, normal blood pressure, and no proteinuria, vWF plasma levels were significantly higher than in a group of 21 healthy volunteers (134% +/- 38% v 80% +/- 22%; P < 0.01). In another group of 16 IgAN patients with normal renal function and proteinuria ranging between 0.3 and 3.8 g/d, vWF levels were also significantly higher than in the control group (148% +/- 63% v 80% +/- 22%; P < 0.001). Afterward, we studied the effects of enalapril administered for 4 weeks on vWF levels and proteinuria in a group of 11 IgAN patients with normal renal function and proteinuria > or = 1 g/d. After 2 weeks on enalapril treatment, both vWF levels and proteinuria had significantly decreased (vWF: 158% +/- 122% to 117% +/- 72%, P < 0.05; proteinuria: 1.6 +/- 0.7 g/d to 0.9 +/- 0.4 g/ d, P < 0.05). After enalapril withdrawal, both vWF and proteinuria significantly increased. A significant correlation between the variations in vWF levels and proteinuria was observed (r = 0.6; P < 0.05). No correlations between blood pressure and changes in vWF or proteinuria were found. We conclude that endothelial dysfunction is observed in patients with IgAN. This abnormality is already present in some patients with normal blood pressure, normal renal function, and absence of proteinuria. Angiotensin-converting enzyme inhibition induced a significant decrease in both vWF levels and proteinuria.