Esculetin (6,7-dihydroxycoumarin) inhibits arachidonic acid 5-lipoxygenase of human polymorphonuclear leukocytes (HPMNL). Complete inhibition of the biosynthesis of 5-HETE, 5,12-DHETE and LTB4 was observed at a concentration of 100 microM (IC50 = = 0.4 microM, 6.0 microM and 0.1 microM, respectively). At these concentrations the formation of the cyclooxygenase product, 12-HHT, is increased. Upon stimulation of the cells with calcium ionophore A-23187, the inhibitory action of esculetin is revealed at the higher concentrations.