AbstractHere we report that genistein, a soybean isoflavone, strongly inhibits tumor promoter‐induced H2O2formation both in vivo and in vitro. Genistein suppressed H2O2production by 12‐O‐tetrade‐canoylphorbol‐13‐acetate‐(TPA) stimulated human polymorphonuclear leukocytes (PMNs) and HL‐60 cells in a dose‐dependent manner over the concentration range 1–150μM. Human PMNs were more sensitive to the inhibitory effect of genistein than HL‐60 cells (50% inhibitory concentration 14.8 and 30.2μM, respectively). In addition, genistein moderately inhibited Superoxide anion formation by HL‐60 cells and scavenged exogenously added H2O2under the same conditions as in cell culture. However, the H2O2‐scavenging effect of genistein was about 50% lower than its inhibition of cell‐derived H2O2formation at all concentrations. In the CD‐1 mouse skin model, genistein strongly inhibited TPA‐induced oxidant formation, edema, and PMN infiltration in mouse skin. Inhibition of TPA‐mediated H2O2in vivo may result from decreased cell‐derived H2O2formation, scavenging of H2O2produced, and/or suppression of PMN infiltration into the dermis. The antioxidant properties of genistein may be responsible for its anticarcinogenic effects, and the dietary availability of genistein makes it a promising candidate for the prevention of human cancers.