The influence of several eicosanoids of the lipoxygenase pathway was examined in anex vivosystem of human whole blood subjected to stimulation by lipopolysaccharide (LPS). Exogenously added leukotriene B4[5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4)] or 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) significantly (P<0.05) enhanced LPS-evoked expression of monocyte tissue factor (TF) activity in a concentration-dependent manner. 15(S)-HETE, on the other hand, exerted such activity only when added at certain concentrations, whereas 5(S)-HETE was devoid of any apparent activity. LPS-induced TF activity was inhibited by the lipoxygenase inhibitors nordihydroguaiaretic acid, CGS 23885 and ZM 230487, by 59, 32 and 88%, respectively. Furthermore, the production of LTB4in LPS-stimulated whole blood was investigated, in the absence or presence of either tumor necrosis factor α (TNFα) or phorbol-12-myristate-13-acetate (PMA). LPS alone induced a moderate time-dependent and concentration-dependent release of LTB4, reaching the maximum concentration (1260 ± 202 pg/ml) within 90 min at 5 ng/ml LPS. The prior and concurrent presence of PMA (5 ng/ml) or TNFα (10 ng/ml) further enhanced the LTB4production approximately twofold (P<0.05). TNFα added alone evoked approximately twice the LTB4production seen when LPS (2200 ± 243 versus 1260 ± 203 pg/ml) was added alone. Considering these results, LPS and TNFα emerge as important agonists of LTB4production in whole blood. LTB4in turn appears to be of importance for the expression of TF in monocytes, potentially amplifying the thrombogenic potential of these cells.