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SUMMARY. We compared alterations of pulmonary hemodynamics with the plasma concentrations of thromboxane B2, 6-keto-PGF la , and PGF20 following intravenous Escherichia coli endotoxin infusion (1 /ig/kg) in three groups of awake sheep. Group 1 served as controls. The animals in group 2 were rendered leukopenic (<1000 WBC/mm 3 ) by nitrogen mustard treatment. Group 3 received ibuprofen (12 mg/kg) one hour before endotoxin. After endotoxin infusion, the pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) increased markedly in groups 1 and 2; however, in group 2, the increases of PAP and PVR were half those of group 1. In group 3, only minimal increases of PAP and PVR were measured. In groups 1 and 2, the rise of PAP correlated with an increased plasma TxB2 concentration at 30 minutes after endotoxin (group 1-from 0.5 ± 0.04 to 16 ± 3 ng/ml; group 2-from 0.32 ± 0.1 to 5.6 ± 1.2 ng/ml). The peak plasma concentrations of TXB2 were significantly less in group 2 than in group 1. In the sheep in both groups 1 and 2, 20 minutes after endotoxin infusion, consistent pulmonary artery to aortic increases of TxB2 were measured (group 1 A3.7 ± 1.1 ng/ml and group 2 A3.1 ± 0.7 ng/ml). In group 3, plasma TxB2 increased slightly to 240 ± 80 pg/ml. Plasma concentrations of 6-keto-PGFi,, increased in group 1 from 0.06 ± 0.01 to 0.59 ± 0.12 ng/ml and in group 2 from 0.06 ± 0.01 to 0.58 ± 0.12 ng/ml. In group 3 sheep, plasma concentrations of 6-keto-PGF ]o remained below the detection limit of the radioimmunoassay. TxA2 is a likely mediator of endotoxin-induced pulmonary hypertension and is generated in large quantities by cells in the lung. Circulating leukocytes contribute substantially to the peak plasma concentrations of thromboxane following endotoxin infusion. (Circ Res 50:688-694, 1982)

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