Prostanoids are biologically active mediators of inflammation and tissue injury. To investigate the role of prostanoids in orthotopic liver transplantation we used a porcine model and determined prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 in arterial, portal, and hepatic venous blood during organ harvesting, the recipient operation, and the early postoperative period. There were no significantly increased serum levels during the donor operation or at the end of cold storage. As early as 1 or 5 min after initiation of reperfusion of the transplanted organ, prostanoids in hepatovenous blood increased dramatically (100-500-fold). Changes in arterial and portal blood (10-50-fold) were less pronounced but still statistically significant. In surviving animals these values returned to normal within 24 hr. The hepatic release of metabolites of the arachidonic acid cascade after liver grafting indicates that the synthesis of prostanoids might contribute to morphological and functional alterations of the transplanted graft. In addition, the increased arterial values of circulating prostanoids may potentially participate in severe cardiovascular, hemostatic, and immunological alterations known to occur after liver transplantation.