Reduction of vitamin K1 2,3-epoxide by rat and human liver vitamin K epoxide reductase is inhibited by N-ethylmaleimide and iodoacetamide. 2. Both enzymes are protected from inhibition by N-ethylmaleimide by vitamin K1 or vitamin K1 2,3-epoxide. 3. Vitamin K1 inhibits reduction of vitamin K1 2,3-epoxide to vitamin K1 which suggests product inhibition of the enzyme.