Previous studies demonstrated that acute infusion of cuprophan activated plasma into experimental animals produce cardiopulmonary changes which included severe pulmonary hypertension. It was further suggested that these changes were mediated by complement activation products. The current study examined the role of arachidonic acid metabolites in the pathogenesis of cuprophan-induced pulmonary hypertension in the swine. Plasma thromboxane concentrations and pulmonary arterial pressure rose concomitantly with cuprophan-activated plasma infusion; both could be inhibited by the specific thromboxane synthetase inhibitor, OKY1581. Likewise, this inhibitor also blocked the increment in plasma thromboxane concentrations and pulmonary arterial pressure induced by zymosan-activated plasma. In vitro incubation of cuprophan-activated plasma with porcine lung fragments produced significantly higher thromboxane concentrations in the medium than incubation with other porcine tissues examined. It is postulated that the complement activation products formed in the plasma during cuprophan exposure subsequently stimulated release of thromboxane from the lungs and other tissues upon infusion of the plasma into animals. The thromboxane, in turn, triggers the pulmonary hypertension.