MCT produces pulmonary vascular injury and pulmonary hypertension in rats by unknown mechanisms and provides a useful animal model with which to study chronic pulmonary hypertension. Several arachidonic acid metabolites including TxA2 and LT are present in increased concentration in lungs of rats made chronically pulmonary hypertensive with MCT or MCTP. The lack of protection afforded by cotreatment with drugs that inhibit the biosynthesis or antagonize the actions of TxA2 indicates that TxA2 does not play a major role in the pathogenesis of cardiopulmonary injury in this model. Results with DEC suggest the possibility of involvement of LT in the response to MCT and MCTP; additional work is needed to clarify the exact role of LT in this model. The roles of other biologically active lipid mediators such as platelet activating factor and HETEs are currently unknown. Increased understanding of the role of various mediators will come partly from the identification and careful use in vivo of improved drugs that have specific effects as synthesis inhibitors or receptor antagonists.