We studied the effects of pretreatment with either ibuprofen (15 mg/kg), diethylcarbamazine (DEC, 15 mg/kg), or vehicle, on the hemodynamic, hematologic, and serum tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 responses to a bolus Escherichia coli endotoxin infusion (2 mg/kg) in 21 pentobarbital-anesthetized dogs (n = 7 each group). Hematologic and cytokine data were collected before and 0.5, 1, and 3 h after endotoxin infusion. Endotoxin decreased arterial pressure (P-a), cardiac output (CO), total leukocyte (WBC) and platelet counts, and increased lactate, TNF-alpha, and IL-6. TNF-alpha levels peaked at 1 h and decreased by 3 h, whereas IL-6 remained elevated. Ibuprofen abolished the endotoxin-induced changes in P-a and lactate, but did not alter the initial decrease in CO, WBC, and platelets or the increase in TNF-alpha and IL-6. DEC did not alter the response to endotoxin, although the DEC group had higher TNF-alpha and IL-6 levers before endotoxin infusion compared to controls. We conclude that the cardiovascular effects of ibuprofen in the canine model of acute endotoxemia are not due to suppression of the systemic inflammatory response.