Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) fo the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, beta-thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non-affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti-urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of beta-thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p less than 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p less than 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.