Excessive production of prostaglandins may be of importance for the development of organ damage in generalized infection. To investigate the role of tumor necrosis factor (TNF) in systemic prostacyclin release in gram-negative septicemia, the plasma concentrations of its stable metabolite 6-keto-prostaglandin F^1α (6-keto-PGF^1α ) were sequentially measured after intravenous bolus injections of recombinant human TNF (50 µg/m²; n = 6) and Escherichia coli endotoxin (2 ng/kg; n = 3) in healthy men. TNF induced a rapid increase in plasma 6-keto-PGF^1α from 0.11 ± 0.01 to 0.44 ± 0.15 ng/ml after 30 min (P < .001). Endotoxin also elicited a rise in plasma 6-keto-PGF^1α, but peak values were reached only after 90 min (from 0.07 ± 0.01 to 0.19 ± 0.04 ng/ml; P < .002). These results indicate that TNF may serve as an intermediate factor in systemic elaboration of prostacyclin in endotoxemia and gram-negative septicemia.