A B S T R A C T We examined the role ofprostaglandins and thromboxanes as mediators of plasma-dependent increased polymorphonuclear leukocyte adhesiveness induced by Escherichia coli lipopolysaccharide. The cyclo-oxygenase inhibitors-indomethacin and d,l-6-chloro-a-methyl-carbozole-2-acetic acid (R020-5720) -reduced lipopolysaccharide-induced adherence of polymorphonuclear leukocytes by 74 and 62%, respectively. In addition, inhibitors of thromboxane synthetase -imidazole, 9,1 1-azoprosta-5,13-dienoic acid, and 1-benzylimidazole-suppressed the stimulation of adherence by 31, 66, and 83%, respectively. Exogenous prostaglandins El, E2, and F2a did not increase polymorphonuclear leukocyte adherence, nor were they detected in significant quantities in supernates of polymorphonuclear leukocytes exposed to lipopolysaccharide. However, inhibitors of both cyclooxygenase and thromboxane synthetase reduced increases in adherence induced by arachidonic acid (10 ,ug/ml), suggesting that lipopolysaccharidemediated increases in adherence were due to an arachidonic acid product other than prostaglandin E2 or F2a. 8,11,14-Eicosatrienoic acid, a precursor of monoenoic prostaglandins, did not enhance polymorphonuclear leukocyte adhesiveness.We next demonstrated lipopolysaccharide-stimulated generation, by polymorphonuclear leukocytes, of a labile, low molecular weight, dialyzable substance capable of enhancing the adherence of unstimulated leukocytes. In parallel experiments, a 10-fold increase Portions of this work have appeared in abstract form:Program