Ibuprofen and the leukotriene antagonist, LY203647, were used to evaluate the effectiveness of LY203647 in the dual blockade of cyclooxygenase and leukotriene to maintain hemodynamic parameters in endotoxemia. Ibuprofen pretreatment alone or dual blockade (ibuprofen plus LY203647) protected blood pressure and renal blood flow at 1 and 3 hr after endotoxin infusion. Cardiac output at 1 hr after endotoxin in dogs treated with ibuprofen was slightly but significantly decreased. Dual pretreatment prevented this decrease at 1 hr; however, cardiac output was similar in both groups by 3 hr. Dual blockade administered after endotoxin induced increases in blood pressure and cardiac output at 3 hr. LY203647 pretreatment alone did not prevent the postendotoxemic declines in any measured parameters. The increased plasma SGOT and lactate of endotoxemia were exacerbated by LY203647 and blunted by ibuprofen treatment. We conclude that the addition of LY203647 to ibuprofen treatment offers no additional significant protection of hemodynamic parameters.