The role of IL-6 as a mediator of haemostatic changes during severe inflammation is controversial. To assess the effect of IL-6 on haemostasis we conducted a controlled cross-over study in eight patients with metastatic renal cell cancer. In all subjects coagulation and fibrinolysis were monitored during and after a 4-h infusion of either 150 μg recombinant human (rh) IL-6, or during infusion of saline (control study). Mean maximum IL-6 concentrations were 1418.0 ± 755.8 pg/ml. Compared to the control study, rhIL-6 induced activation of coagulation as reflected by a 190 ± 55% increase in the plasma levels of thrombin-antithrombin III complexes (p <0.001) and by a 24 ± 11% increase in the plasma levels of in the prothrombin activation fragment F1 + 2 (p <0.001). In contrast, fibrinolysis was not affected. We conclude that in severe inflammation IL-6 may contribute to the activation of coagulation, whereas other factors mediate changes in fibrinolysis.