The addition of sera from patients with collagen diseases, particularly those with vascular complications, to the supernatant of cultured vascular endothelial cells (EC) in vitro significantly increased the surface and intracellular amounts of von Willebrand factor antigen (vWF:Ag) compared with results obtained with sera from normal healthy subjects. Peak levels of vWF:Ag occurred after 24 h of in vitro culture. Moreover, the amounts of vWF:Ag secreted into the EC supernatant with patient serum added were significantly higher than the amounts secreted into EC supernatant with control serum added, even after 48 h of in vitro culture. Levels of large and intermediate multimers (LIM) of von Willebrand factor (vWF) increased in EC supernatant exposed to serum from patients with collagen diseases as compared with levels in supernatant exposed to serum from normal controls, whereas no significant differences were detected overall between adding the plasma of patients and of normal subjects. In addition, C-reactive protein (CRP) induced a time- and dose-related release of vWF:Ag from EC, while glucocorticoid did not effect the release of vWF:Ag from EC. These results suggest that the sera of patients with collagen diseases, particularly those with vascular complications, stimulate the production and release of LIM of vWF from EC.