Hinokitiol (4-isopropyltropolone), a constituent of Japanese cypress, reversibly inhibited platelet-type 12-lipoxygenase with an IC50 of 0.1 mu M, and the enzyme activity was almost lost at 1 mu M The compound was much less active with other lipoxygenase enzymes with higher IC50 values (leukocyte-type 12-lipoxygenase, 50 mu M; soybean lipoxygenase, 17 mu M; 15-lipoxygenase-1, >100 mu M; 5-lipoxygenase, 17 mu M). Hinokitiol up to 100 mu M had almost no effect on cyclooxygenases-1 and -2. Their structure-activity relationship examined with various tropolone derivatives indicated the requirements of the g-hydroxyl group and 4-alkyl group for the potent and selective inhibition of platelet-type 12-lipoxygenase,