Early infections and wound healing disorders after implantation of a total knee replacement occur regardless of the intraoperative use of a tourniquet. The biochemical regulatory processes responsible for the disturbances in microcirculation and thus the potential therapeutic options have yet to be elucidated. The hypothesis of the present paper was that endothelin-1 (ET-1), a mediator of microcirculation disturbances in parenchymatous organs, also is released after major operations on peripheral joints. The concentration of ET-1 in the plasma was determined preoperatively and at 10 postoperative time points (5 min-48 h) with (group A, n=10) and without the use of a tourniquet (group B, n=10). The ET-1 concentration achieved its maximum 6h after opening the tourniquet, which corresponded to 3.3 times the preoperative value. Without a tourniquet, the concentration maximum (2.9 times the baseline value) was achieved already 1.5 h after the end of the operation. However, the total amount of ET-1 secreted over 24 h was identical in both groups (p>0.5). We conclude that the tissue hypoxia resulting from the use of a tourniquet modulates ET-1 secretion, but that traumatization during the operation has a much stronger influence on the total amount secreted. ET-1 antagonists thus should be discussed for the drug prophylaxis of wound healing disorders, regardless of the use of a tourniquet.