The antioxidant nordihydroguaiaretic acid (NDGA) is a plant phenolic lignan originally isolated from the creosote bush (Larrea tridentata). It has been shown that NDGA scavenges efficiently hydroxyl radicals (center dot OH). In the present paper the mechanism by which NDGA scavenges center dot OH is addressed performing a combined experimental and theoretical investigation. We found that NDGA protects, in a concentration-dependent way, bovine serum albumin and DNA from the damage induced by center dot OH generated by the Fenton reaction. In addition, the NDGA + center dot OH reaction is predicted to be diffusion-controlled. The first step of this reaction is proposed to occur mainly by a sequential electron proton transfer from NDGA to center dot OH generating a neutral radical of NDGA, which after a second oxidation step gives a diradical that after a cascade sequential complex reaction produces a cyclic compound. This cyclic product is predicted to have a UV-vis spectrum very similar to that of NDGA, making its identification by this technique very difficult. The electrochemical studies performed in water support the formation of a cyclic compound (C2) as the main product of the reaction. It is concluded that NDGA can scavenge at least two center dot OH.