AbstractArachidonic acid can be oxidized via the cyclooxygenase pathway to produce prostaglandins and via the 5−lipoxygenase pathway to produce leukotrienes. These substances are known to be extremely potent regulators of cellular function in somatic tissues, particularly during inflammatory reactions. Recent studies have implicated cyclooxygenase−derived products in preventing polyspermy in sea urchins [Schuel et al, Gamete Res 10:9–19, 1984]. FPL−55712, a receptor antagonist for leukotrienes in somatic tissues, causes a dose−(1–10 μM) and sperm−density−dependent induction of polyspermic fertilization in sea urchins if added before the egg completes the cortical reaction (elevation of the fertilization envelope). Eggs pretreated with FPL−55712 become polyspermic upon subsequent insemination with untreated sperm in sea water. Sperm pretreated with the drug do not cause polyspermy when used to inseminate untreated eggs. The 5−lipoxygenase inhibitor BW775C also promotes polyspermy. FPL−55712 and BW755C do not retard elevation of the fertilization envelope. These findings imply that (1) leukotrienes may be produced via the 5−lipoxygenase pathway during fertilization in sea urchins, and (2) the reaction of leukotrienes with putative receptors on the egg's surface may modulate its receptivity to sperm during the cortical reaction, and thereby