Von Willebrand factor activity and factor VIII/von Willebrand factor (fVIII/vWf) antigen concentrations were evaluated in 17 patients with scleroderma, nine patients with Raynaud's phenomenon, and eight control volunteers. Higher circulating levels of both activities were seen: von Willebrand factor, 374% +/- 40% (percent of control values) in scleroderma patients, 502% +/- 104% in patients with Raynaud's phenomenon and 102% +/- 6% in control subjects (p less than 0.005, scleroderma versus control): fVIII/vWf antigen, 255% +/- 24% in scleroderma patients; 271% +/- 46% in patients with Raynaud's phenomenon, and 99% +/- 4% in control subjects (p less than 0.005, scleroderma versus control). Because endothelial cells synthesize and secrete both substances, the role of endothelial injury in vitro was investigated. Wound injury induced a 344% +/- 33% increase in von Willebrand factor and a 115% +/- 5% increases in fVIII/vWf antigen; cold injury induced 644% +/- 66% and 150% +/- 10% increases, and cytotoxic endothelial injury induced 1055% +/- 83% and 185% +/- 20% increases. In five patients with scleroderma, cold exposure led to a further increase in both activities. The observed increase of both activities in scleroderma and Raynaud's phenomenon may reflect in-vivo endothelial injury and regeneration in these related conditions.